Facially amphiphilic polymers as anti-infective agents

ABSTRACT

Facially amphiphilic polymers and articles made therefrom having biocidal surfaces are disclosed. The polymers can inhibit the growth of microorganisms in contact with the surface or in areas adjacent to said biocidal surface. There is also disclosed a method to identify and optimize the facial amphiphilicity of polyamide, polyester, polyurea, polyurethane, polycarbonate and polyphenylene polymers. Utility as a contact disinfectant is disclosed.

REFERENCE TO PREVIOUS APPLICATIONS

[0001] This application claims priority to U.S. Provisional PatentApplication Ser. No. 60/274,145 filed Mar. 8, 2001.

GOVERNMENT SUPPORT

[0002] This invention was supported in part by funding from the U.S.Government (NSF Grant DMR00-79909) and the U.S. Government may thereforehave certain rights in the invention.

FIELD OF THE INVENTION

[0003] The present invention relates to the design and synthesis offacially amphiphilic polymeric compounds with microbiocidal propertiesthat can be coated on or incorporated into materials and methods todesign the same. The present invention further relates to methods toidentify and design facially amphiphilic polymers and methods to preventor limit microbial growth.

BACKGROUND OF THE INVENTION

[0004] Amphiphilic molecules exhibit distinct regions of polar andnonpolar character. These regions can result from substitution ofhydrophobic and hydrophilic substituents into specific and distinctregions of conformationally defined molecules. Alternately aconformationally flexible molecule or macromolecule can adopt an orderedstructure in which the hydrophobic and hydrophilic substituents on themolecule segregate to different areas or faces of the molecule. Commonlyoccurring amphiphilic molecules include surfactants, soaps, detergents,peptides, proteins and copolymers. These molecules have the capacity toself-assemble in appropriate solvents or at interfaces to form a varietyof amphiphilic structures. The size and shape of these structures varieswith the specific composition of the amphiphilic molecule and solventconditions such as pH, ionic strength and temperature.

[0005] Amphiphilic peptides with unique broad-spectrum antimicrobialproperties have been isolated fiom a variety of natural sourcesincluding plants, frogs, moths, silk worms, pigs and humans (H. G. BomanImmunol Rev. 2000 173:5-16; R. E. Hancock and R. Lehrer, TrendsBiotechnol. 1998 16:82-88). These compounds include the magainin 1 (1)and dermaseptin S1 (2) isolated from the skin of frogs and the cecropinA (3) isolated from the cecropia moth. These naturally occurringcompounds have broad-spectrum antibacterial activity and they do notappear prone to the development of bacterial resistance. These compoundsare relatively low molecular weight peptides that have a propensity toadopt α-helical conformation in hydrophobic media or near a hydrophobicsurface and as a result are facially amphiphilic (i.e., one-third totwo-thirds of the cylinder generated by the helical peptide hashydrophobic side chains while the GIGKFLHSAGKFGKAFVGEIMKS-CO₂H (1)ALWKTMLKKLGTMALHAGKAALGAAADTISQGTQ-CO₂H (2)KWKLFKKIEKVGQNIRDGIIKAGPAVAVVGQATQIAK-NH₂ (3) RGGRLCYCRRRFCVCVGR-NH₂ (4)

[0006] remainder has hydrophilic side chains. These hydrophilic sidechains are primarily positively-charged at neutral pH. Hydrophobic aminoacids compose 40-60% of the total number of residues in mostanti-microbial peptides. The selectivity of the amphiphilic peptides(e.g. for bacteria vs. human erythrocytes) depends on the overallhydrophobicity. The biological activity of thee compounds depend on theratio of charged (c) to hydrophobic (h) residues. When the ratio isvaried from 1:1 (c:h) to 1:2 (c:h) peptides with more hydrophobicresidues tend to be more active toward erythrocyte membranes. Thephysiochemical properties rather than the presence of particular aminoacids or the tertiary structure of the side chains. Related peptideshave been isolated from mammals and these anti-microbial peptides havebeen suggested to be an important component of the innate immuneresponse. (Gennaro, R. et al. Biopoylmers (Peptide Science) 2000, 55,31)

[0007] These observations recently have been extended to peptides(β-peptides) comprised of β-amino acids. These non-natural polypeptidemimetics also are capable of adopting stable α-helical and β-sheetstructures although the precise geometries of these structure aredifferent form those generated by α-amino acid oligomers. However,appropriate positioning of hydrophobic and hydrophilic residues resultsin amphiphilic conformations with similar antimicrobial properties. Thisfurther confirms the importance of repeating periodicity of hydrophobicand hydrophilic groups vis-à-vis the precise amino acid sequence inproducing facial amphiphilic antimicrobial compounds. (D. Seebach and J.L. Matthews, Chem Commun. 1997 2105; Hamuro, Y., Schneider, J. P.,DeGrado, W. F., J. Am. Chem. Soc. 1999, 121, 12200-12201; D. H. Appellaet al., J. Am. Chem. Soc., 1999 121, 2309)

[0008] Secondary structures other than helices may also give rise toamphiphilic compounds. The protegrins (4) are a related series ofanti-microbial peptides. (J. Chen et al., Biopolymers (Peptide Science),2000 55 88) The presence of a pair of disulfide bonds between Cys⁶-Cys¹⁵and Cys⁸-Cys¹³ results in a monomeric amphiphilic anti-parallel β-sheetformed by the chain termini and linked by a β-turn. The amphiphilicβ-sheet conformation is essential for anti-microbial activity againstboth gram-positive and gram-negative bacteria.

[0009] The data related to anti-microbial peptides suggests that facialamphiphilicity, the alignment of polar (hydrophilic) and nonpolar(hydrophobic) side chains on opposite faces of a secondary structuralelement formed by the peptide backbone, and not amino acid sequence, anyparticular secondary/tertiary structure, chirality or receptorspecificity is responsible for their biological activity

[0010] Suitably substituted polymers which lack polyamide linkages alsoare capable of adopting amphiphilic conformations. Solid phase chemistrytechnology was utilized to synthesize a class of meta substitutedphenylacetylenes that fold into helical structures in appropriatesolvents (J. C. Nelson et al., Science 1997 277:1793-96; R. B. Prince etal., Angew. Chem. Int. Ed. 2000 39:228-231). These molecules contain anall hydrocarbon backbone with ethylene oxide side chains such that whenexposed to a polar solvent (acetonitrile), the backbone would collapseto minimize its contact with this polar solvent. As a result of the metasubstitution, the preferred folded conformation is helical. This helicalfolding is attributed to a “solvophobic” energy term; although, theimportance of favorable π-π aromatic interactions in the folded stateare also likely to be important. Furthermore, addition of a less polarsolvent (CHCl₃) results in an unfolding of the helical structuredemonstrating that this folding is reversible.

[0011] Regioregular polythiophenes (5 and 6) have been shown to adoptamphiphilic conformations in highly ordered π-stacked arrays withhydrophobic side chains on one side of the array and hydrophilic sidechains on the other side. These polymers form thin films useful in theconstruction of nanocircuits. (Bjørnholm et al., J. Am. Chem. Soc., 1998120, 7643) These materials would be facially amphiphilic as definedherein; however, no biological properties have reported for thesecompounds.

[0012] Antimicrobial peptides have been incorporated onto surfaces orbulk materials, with some retention of antimicrobial properties. Haynieand co-workers at DuPont have investigated the activity of Antibacterialpeptides have been covalently attached to solid surfaces (S. L. Haynieet al., Antimicrob Agents Chemother, 1995 39:301-7; S. Margel et al., JBiomed Mater Res, 1993, 27:1463-76). A variety of natural and de novodesigned peptides were synthesized and tested for activity while stillattached to the solid support. The activity of the peptides decreasedwhen attached to the solid support although the peptides retained theirbroad spectrum of activity. For example, a de novo designed peptidereferred to as E14LKK has a MBC (minimum bactericidal activity) of 31μg/ml in solution as opposed to 1.5 mg/ml when attached to a solid phasebead. The peptides were attached to the resin with a 2 to 6-carbon alkyllinker. The porosity of Pepsyn K, the resin used in the synthesis, issmall (0.1 to 0.2 μm) compared to the bacteria, so the microbes may beunable to penetrate into the interior of the resin. Thus the greatmajority of the peptide would not be available for binding to cells. Theantimicrobial activity did not arise from a soluble component; noleached or hydrolyzed peptide was observed and the soluble extracts wereinactive. These studies indicate quite convincingly that antimicrobialpeptides retain their activity even when attached to a solid support.However, there is a need to optimize the presentation of the peptides toincrease their potency.

[0013] Other antimicrobial polymeric materials have been reported whichcontain chemical functionality known to be antimicrobial (J. C. Tilleret al., Proc Natl Acad Sci U S A, 2001 98:5981-85). A large portion ofthis work uses chemical functions such as alkylated pyridiniumderivatives, which are known to be toxic to mammalian cells. Theantibiotic ciprofloxacin has been grafted into a degradable polymerbackbone (G. L. Y. Woo, et al., Biomaterials 2000 21:1235-1246). Theactivity of this material relies on cleavage of the active componentfrom the polymer backbone.

[0014] Anti-infective vinyl copolymers, wherein monomers withhydrophobic and hydrophilic side chains have been randomly polymerizedto produce polymers with amphiphilic properties, have also beendescribed recently W. H. Mandeville III et al. (U.S. Pat. No.6,034,129). These materials are produced by polymerization ofhydrophobic and hydrophilic acrylate monomers. Alternately, thehydrophobic side chain is derived from a styrene derivative which iscopolymerized with a hydrophilic acrylate monomer wherein an ionic groupis linked to the carboxylic acid. These polymers, however, haverelatively random arrangements of polar and nonpolar groups and are notfacially amphiphilic as defined herein.

[0015] An alternative method to make amphiphilic polymers is to produceblock copolymers comprised of hydrophobic blocks (A) and hydrophilicblocks (B), commonly polypropyleneoxy and polyethylenoxy segmentsrespectively, into A-B, A-B-A or similar copolymers. These copolymersalso are not facially amphiphilic as defined herein.

BRIEF DESCIRPTION OF FIGURES BRIEF DESCRIPTION OF THE DRAWINGS

[0016] Specific embodiments of the invention have been chosen for thepurpose of illustration and description but are not intended in any wayto restrict the scope of the invention. These embodiments are shown inthe accompanying drawings wherein:

[0017] In FIG. 1 there is shown a cartoon that depicts the separation ofhydrophobic and hydrophilic side chains onto opposite faces of thepolymer backbone.

[0018] In FIG. 2 there is shown the general structure of a faciallyamphiphilic polyamide or polyester copolymer formulae I and II,representative monomer units for aromatic polyamides, Ia and Ia, the tworepresentative monomer units for polyamides with both aromatic andaliphatic components, Ib and IIb.

[0019] In FIG. 3 there is shown the general structure of polyamides withextended linking groups between the monomers.

[0020] In FIG. 4 there is shown the general structure IV of a faciallyamphiphilic polyurea, polycarbonate and polyurethane copolymers andrepresentative monomer units IVa, IVb and IVc, respectively. Examples oftwo typical polyurea monomers are exemplified in IVd and IVe.

[0021] In FIG. 5 there is shown the complete structure of a faciallyamphiphilic polyamide IId and polyurethane IVf.

[0022] In FIG. 6 there is shown typical examples of ortho- andmeta-phenylene facially amphiphilic polymers XII and XIII respectivelyderived from salicylamide and anthranilimide.

[0023] In FIG. 7 there is shown the synthesis of substituted salicylicand anthranilic acid monomers of XII and XIII

[0024] In FIG. 8 there is shown the synthesis of polyureas XIa-XIc.

[0025] In FIG. 9 there is shown antimicrobial data for polyamide andpolyurea oligomers

[0026] In FIG. 10 there is shown antimicrobial data for polyamideoligomers of general formula VII.

[0027] In FIG. 11 there is shown the time course for antibacterialactivity of a polyurea oligomer.

SUMMARY OF THE INVENTION

[0028] One object of the invention is to provide new polymeric compoundswith anti-microbial properties which can be applied to or dispersedthroughout devices, articles and surfaces and which are capable ofkilling microorganisms on contact, but leach into the environment moreslowly than traditional small molecule anti-microbials. The polymericmaterials may be deposited as a film on the surface of a substrate ormay be dispersed

[0029] throughout a substrate to provide an anti-microbial surface. Thepolymeric materials of the present invention are anti-microbial polymersthat are designed to possess amphiphilic properties in the presence ofmicrobial cell walls and to disrupt the membrane and kill the organism.The polymeric materials are further designed to have low toxicity tomammalian cells.

[0030] The facially amphiphilic polymers of the present invention arepolyamide or polyester compounds of formulae I and II wherein x is O,NR³ or S, y is CO, CS or SO₂ and A and B are aromatic, heteroaromatic oraliphatic moieties appropriately substituted with polar and nonpolargroups; polyurea, polycarbamate, or polycarbonates compounds of formulaeIV wherein x and y are O, NR³ or S, z is CO, CS or SO₂ and A and B arearomatic, heteroaromatic or aliphatic moieties appropriately substitutedwith polar and nonpolar groups; and polyphenylene and heteroarylenecompounds of formula V wherein is either a single bond, double bond,triple bond or absent and A and B are aromatic, heteroaromatic moietiesappropriately substituted with polar and nonpolar groups. R, R¹ and R²are end groups appropriate for the specific polymer chain and theirdesign is well know in the polymer art.

[0031] These facially amphiphilic polymers are capable of adoptingrepeating secondary structural motifs that allow for the segregation ofpolar and nonpolar regions of the molecule into different spatialregions. The anti-microbial polymers adopt amphiphilic conformationswhen placed in contact with the cell walls of microorganisms and theamphiphilic molecules are capable of disrupting essential cell wallfunctions resulting in the death of the microorganism.

[0032] The present invention further provides methods for killingmicroorganism on surfaces by disposing thereon a facially amphiphilicpolymer. The method for making compositions incorporating the faciallyamphiphilic polymers includes providing a solution dispersion orsuspension of the polymer and applying it to the surface. Alternatelycompositions can be prepared by incorporating the polymer into plasticsthat subsequently are molded, shaped or extruded into other articles.The optimal method to deliver the polymer will depend on several factorsincluding the desired coating thickness and the nature and configurationof the substrate and the physical characteristics of the faciallyamphiphilic polymer.

[0033] The facially amphiphilic polymers of the present invention canhave a substantial range in molecular weight. Facially amphiphilicmolecules with molecular weights of about 0.8 kD to about 20 kD will bemore prone to leach from the surface of the substrate. The faciallyamphiphilic polymer may be attached or immobilized on the substrate byany appropriate method including covalent bonding, ionic interaction,coulombic interaction, hydrogen bonding or cross-linking. The polymersof the present invention provide a surface-mediated microbiocide thatonly kills organisms in contact with the surface. Moreover the polymersof the present invention are stable and retain their bioactivity forextended periods of time and are nontoxic to birds, fish, mammals andother higher organisms.

[0034] The present invention further provides a computational techniqueto evaluate the energy of polymer conformations and identify polymerswhich have the capability of exhibiting amphiphilic behavior and aid inidentifying optimal sites for substitution of polar and nonpolarsubstituents that confer amphiphilic properties.

DETAILED DESCRIPTION OF THE INVENTION

[0035] Microbial infections represent a serious continuing problem inhuman and animal health. While amphiphilic α and β-peptides exhibitpotent antibacterial, they are, nevertheless, difficult and expensive toprepare in large quantities. Peptides are sensitive to enzymatic andchemical hydrolysis. Exposure to microbial pathogens can occur in avariety of ways. Most objects encountered daily have the potential forharboring infectious organisms and new compounds and approaches forcontrolling the growth of microbes are extremely valuable and havesignificant commercial potential. Antimicrobial peptides related to themagainins have desirable biological activities but their utility islimited. An object the present invention is to provide new stableantimicrobial polymers which are available from inexpensive and readilyavailable monomers and which can be incorporated into, or on to, a widevariety of materials and can withstand chemical and enzymaticdegradation.

[0036] In recent years, the design of non-biological polymers withwell-defined secondary and tertiary structures (S. H. Gellman et al.,Acc. Chem. Res. 1998 31:173-80; A. E. Barron and R. N. Zuckerman, Curr.Opin. Chem. Biol., 1999 3:681-687; K. D. Stigers et al., Curr. Opin.Chem. Biol., 1999 3:714-723) has become an active area of research. Onereason for this interest is that for the first time, modem methods ofsolid phase organic chemistry (E. Atherton and R. C. Sheppard, SolidPhase Peptide Synthesis A Practical Approach IRL Press Oxford 1989) haveallowed the synthesis of homodisperse, sequence-specific oligomers withmolecular weights approaching 5,000 Daltons. The development of this newfield of homodisperse sequence-specific oligomers promises to generatemolecules with novel chemical and physical properties that will span thegap between polymer and protein science. Polymers are statisticalmixtures of molecules typically composed of one to a few monomers. Bycontrast, peptides and proteins are molecules typically composedfrom >15 monomers with exact control over sequence, topology, andstereochemistry. These homodisperse sequence-specific oligomersrepresent molecules with features of both polymers and proteins

[0037] Facially amphiphilic polymers can be homopolymers wherein onemonomer is substituted with both a nonpolar and a polar substituent orcopolymers wherein one monomer is substituted with a polar substituentand the other monomer is substituted with a nonpolar substituent. Sincethe antimicrobial activity arises from the amphiphilic characterconferred by a periodic pattern of side chains rather than the precisespatial arrangement of side chains, other substitution patterns are alsoexpected to produce facially amphiphilic polymers and they all areencompassed by the present invention. (see FIG. 7)

[0038] Polyamide and polyester homopolymers and copolymers of thepresent invention (FIG. 1) can be comprised solely of aromatic orheteroaromatic monomers or may include both aromatic and aliphaticmonomers. One embodiment of the invention is a copolymer with aromaticmonomers and α-amino acid monomers. The polyamides and polyesters can beconstructed either by repetitively linking amino (or hydroxy) acidmonomers (FIG. 1, I) or by alternating diamine (or dihydroxy) anddicarboxylic acid monomers (FIG. 1, II). While the majority of aromaticrings in the examples depicted in FIGS. 1 and 2 have a meta substitutionpattern, one skilled in the art would immediately appreciate thatequivalent polymers could be designed with an ortho or a paraorientation and these modifications can alter the conformation and thephysical properties of the resulting polymer. Furthermore although thecopolymers in FIG. 1 Ia and Ila-IIc are depicted with one polar and onenonpolar substituent, other substitution patterns are equally plausible.The optimal substitution patterns are determined by the conformationalproperties of the polymer backbone.

[0039] While polyamides and polyesters are the most common occurringexamples of the present invention, other functional groups can beincorporated into the polymer backbone with similar results. Inparticular, thioamides and thioesters are anticipated to have verysimilar properties. The distance between aromatic rings cansignificantly impact the geometrical pattern of the polymer and thisdistance can be altered by incorporating aliphatic chains of varyinglength (FIG. 1, IIc). Although IIc is depicted as a unsubstantiatedalkylene chain, the alkylene chain can be optionally substituted or cancomprise an amino acid, a dicarboxylic acid or a diamine. The distancebetween and the relative orientation of monomers also can altered byreplacing the amide bond with a surrogate with additional atoms (FIG. 2,XV-XVII). Thus replacing the carbonyl group with a dicarbonyl alters thedistance between the monomers and the propensity of dicarbonyl unit toadopt an anti arrangement of the two carbonyl moiety and alter theperiodicity of the polymer. Pyromellitic anhydride (FIG. 2, IVg)represents still another alternative to simple amide linkages which cansignificant alter the conformation and physical properties of thecopolymer (FIG. 1, IVb).

[0040] The synthetic processes can be modified to produce differentranges in molecular weight and the anti-microbial polymer of the presentinvention will have a molecular weight selected to impart physical andchemical properties optimized for the particular application beingcontemplated. Traditional polymer syntheses produce a product with arange of molecular weights. The polymer chemist will readily appreciatethat the chain length of these polymers can be varied by techniques knowin the polymer art. Polymers of the present invention can range inmolecular weight from about 800 Daltons up to about 350 kiloDaltons.Advancements in solid-phase and solution phase synthesis of amino acidoligomers have made available techniques to prepare homogeneous polymersor oligomers with defined sequence and size and these techniques can beadapted to the present invention.

[0041] Polyureas (FIG. 3, IVa), polycarbonates (FIG. 3, IVb) orpolyurethanes (FIG. 3, IVc) are carbonic acid derivatives and exhibitproperties similar to polyamides (N. Samson et al. J. Appl. Polym. Sci.65, 2265 (1997)). FIG. 3 IVd and IVe depict two different substitutionpatterns which can be utilized. Other substitution patterns are equallyeffective.

[0042] The polymer design process simply requires a structure in whichthe repeating sequence of monomers matches the secondary structureadopted by the backbone. Once the periodicity is observed, monomerssubstituted with polar and nonpolar groups monomers must be prepared andintroduced to produce a cationic, amphiphilic secondary. Aromaticpolyamides and ureas frequently have only a few torsional degrees offreedom per repeat (typically two or four). In this case the secondarystructure adopted by these polymers is most likely planar with polar andnonpolar groups extended from opposite sides of the backbone. In somecases, the desired facial amphiphilicity can be achieved through asimple design principal.

[0043] Additional molecular features can be added to the macromolecularbackbone to promote the desired secondary structure and disfavor otherstructures thereby combining elements of both positive and negativedesign. Conformational studies on biofoldamers (proteins and RNA), andearly work with a variety of sequence-specific polymers, have shown thatseveral elements are crucial in order for the polymers to adopt thedesired folded conformation. Key elements include strong electrostaticinteractions (i.e., intramolecular hydrogen bonding) between adjacent ormore distant monomers and rigidification caused by the backbone torsionsor by bulky functional groups. For example, the presence of multiplehydrogen bond donors and acceptors along the macromolecular backbone canlead to extensive intermolecular backbone interactions. Preciseplacement of well designed intramolecular interactions can stabilizedesired secondary structures while at the same time blocking thebackbone hydrogen bond donors which limits intermolecular aggregationproblems. For example, in the polyurea and polyamide a thioether (FIG.3, XIa-c) was positioned between the two aromatic nitrogens to form aninternal hydrogen bond between the sulfur and urea function. This limitsthe torsional angle of the aromatic carbon-urea NH bond by forcing theNH group to be on the same side as the heteroatom, thereby helping todefine the overall sheet-like secondary structure. The secondarystructure for this backbone is predicted to be nearly planar. Similarly,the poly-anthranilate polymer (XIII) is designed based on the finding ofHamuro and Hamilton (Y. Hamuro et al., J. Am. Chem. Soc. 1996119:10587-93) that intramolecular hydrogen-bonding defines the secondarystructure of this class of poly-arylamides.

[0044] Magainin and the other naturally occurring antibacterial peptidesexhibit considerable variation in their chain length, hydrophobicity anddistribution of charges. These linear peptides do, however, containpositively charges amino acids and a large hydrophobic moment resultingin a high propensity to adopt α-helical conformations in a hydrophobicenvironment, e.g., a cell surface or a natural or synthetic membrane.(Z. Oren and Y. Shai Biopolymers (Peptide Science), 1998 47, 451-463.)The periodic distribution of hydrophobic and hydrophilic side chains intheir amino acid sequences allows the segregation of the hydrophobic andhydrophilic side chains to opposite faces of the cylinder formed by thehelix. The overall amphiphilicity, not the specific sequence, secondarystructure or chirality, correlates best with anti-microbial activity.Thus it appears that any suitably amphiphilic material (not necessarilyan α-helix or β-sheet) would have anti-microbial properties. Thenecessary condition for forming a facially amphiphilic structure is themolecule should have a repeating pattern of polar and nonpolar sidechains whose periodicity is approximately the same as that of thesecondary structure of interest.

[0045] The term “microorganism” as used herein includes bacteria, algae,fungi, yeast, mycoplasmids, parasites and protozoa.

[0046] The term “antimicrobial”, “microbiocidal” or “biocidal” as usedherein means that the materials inhibit, prevent, or destroy the growthor proliferation of microorganisms. This activity can be eitherbacteriocidal or bacteriostatic. The term “bacteriocidal” as used hereinmeans the killing of microorganisms. The term “bacteriostatic” as usedherein means inhibiting the growth of microorganisms which can bereversible under certain conditions.

[0047] The term “polymer” as used herein refers to a macromoleculecomprising a plurality of repeating units or monomers. The term includeshomopolymers, which are formed from a single type of monomers andcopolymers that are formed from two or more different monomers. Incopolymers the monomers may be distributed randomly (random copolymer),in alternating fashion (alternating copolymer) or in blocks (blockcopolymer). The polymers of the present invention are eitherhomopolymers or alternating copolymers. The term “polymer” as usedherein is intended to exclude proteins, peptides, polypeptides and otherproteinaceous materials composed exclusively of α or β-amino acids. Theterm “oligomer” as used herein refers to a homogenous polymer with adefined sequence and molecular weight.

[0048] The term “polymer backbone” or “backbone” as used herein refersto that portion of the polymer which is a continuous chain comprisingthe bonds formed between monomers upon polymerization. The compositionof the polymer backbone can be described in terms of the identity of themonomers from which it is formed without regard to the composition ofbranches, or side chains, off the polymer backbone.

[0049] The term “polymer side chain” or “side chain” refers to portionsof the monomer which, following polymerization, forms an extension offthe polymer backbone. In homopolymers all the polymer side chains arederived from the same monomer. A copolymer can comprise two or moredistinct side chains from different monomers.

[0050] The term “alkyl” as used herein denotes a univalent saturatedbranched or straight hydrocarbon chain. Unless otherwise stated suchchains contain from 1 to 18 carbon atoms. Representative of such alkylgroups are methyl, ethyl, propyl, iso-propyl, sec-butyl, tert-butyl,pentyl, neo-pentyl, iso-pentyl, hexyl, iso-hexyl, heptyl, octyl, nonyl,decyl, tridecyl, tetradecyl, hexadecyl octadecyl, and the like. Whenqualified by “lower” the alkyl group will contain from 1 to 6 carbonatoms. The term “cycloalkyl” as used herein denotes a univalent cyclichydrocarbon chain. Representative groups are cyclopropyl, cyclobutyl,cyclohexyl, cyclopentyl and cyclohexyl.

[0051] The phrase “groups with chemically nonequivalent termini” refersto functional groups such as esters amides, sulfonamides andN-hydroxyoximes where reversing the orientation of the substituents,e.g. R¹C(═O)OR² vs. R¹O(O═)CR², produces unique chemical entities.

[0052] The term “basic heterocycle” as used herein denotes cyclic atomicarray which includes a nitrogen atom that has a pKa greater than about 5and that is protonated under physiological conditions. Representative ofsuch basic heterocycles are pyridine, quinoline, imidazole, imidazoline,cyclic guanidines, pyrazole, pyrazoline, dihydropyrazo line,pyrrolidine, piperidine, piperazine, 4-alkylpiperazine, and derivativesthereof such as 2-aminopyridine, 4-amninopyridine, 2-aminoimidazoline,4-aminoimidazoline or VII where X¹ is O, N, S or absent and i is 2 to 4.

[0053] The term “amphiphilic” as used herein describes athree-dimensional structure having discrete hydrophobic and hydrophilicregions. An amphiphilic polymer requires the presence of bothhydrophobic and hydrophilic elements along the polymer backbone. Thepresence of hydrophobic and hydrophilic groups is a necessary, but notsufficient, condition to produce an amphiphilic molecule or polymer.Polymers frequently adopt a random or disordered conformation in whichthe side chains are located randomly in space and there are nodistinctive hydrophobic and hydrophilic regions.

[0054] The term “facially amphiphilic” or “facial amphiphilicity” asused herein describes polymers with polar (hydrophilic) and nonpolar(hydrophobic) side chains that adopt conformation(s) leading tosegregation of polar and nonpolar side chains to opposite faces orseparate regions of the structure. This structure can comprise any ofthe energetically accessible low-energy conformations for a givenpolymer backbone. Additionally random or block copolymers may adoptrandom backbone conformations that do not lead to distinct hydrophilicand hydrophobic regions or which do not segregate along different facesof the polymer. These copolymers are not facially amphiphilic as definedherein.

[0055] The term “naturally occurring amino acids” means the L-isomers ofthe naturally occurring amino acids. The naturally occurring amino acidsare glycine, alanine, valine, leucine, isoleucine, serine, methionine,threonine, phenylalanine, tyrosine, tryptophan, cysteine, proline,histidine, aspartic acid, asparagine, glutamic acid, glutamine,carboxyglutamic acid, arginine, omithine and lysine. Unless specificallyindicated, all amino acids referred to in this application are in theL-form.

[0056] The term “side chain of a naturally occurring amino acid” as usedherein refers to the substituent on the a-carbon of a amino acid. Thetern “polar side chain of a naturally occurring amino acid” refers tothe side chain of a positively charged, negatively charged orhydrophilic amino acid. The term “nonpolar side chain of a naturallyoccurring amino acid” refers to the side chain of a hydrophobic aminoacid.

[0057] The term “positively charged amino acid” or “cationic amino acid”as used herein includes any naturally occurring or unnatural amino acidhaving a positively charged side chain under normal physiologicalconditions. Examples of positively charged naturally occurring aminoacids are arginine, lysine and histidine.

[0058] The term “hydrophilic amino acid” means any amino acid having anuncharged, polar side chain that is relatively soluble in water.Examples of naturally occurring hydrophilic amino acids are serine,threonine, tyrosine, asparagine, glutamine, and cysteine.

[0059] The term “hydrophobic amino acid” means any amino acid having anuncharged, nonpolar side chain that is relatively insoluble in water.Examples of naturally occurring hydrophobic amino acids are alanine,leucine, isoleucine, valine, proline, phenylalanine, tryptophan andmethionine.

[0060] One embodiment of the present invention is a polymeric compoundof formula I

[0061] wherein:

[0062] x is NR³, O, or S, y is C═O, C═S, O═S═O, or —C(═O)C(═O)— and R³is hydrogen, methyl or ethyl;

[0063] either both A and B are independently optionally substituted o-,m-, p-phenylene, or optionally substituted heteroarylene wherein (i) Aand B are both substituted with a polar (P) group and a nonpolar (NP)group, (ii) one of A and B is substituted with a polar (P) group and anonpolar (NP) group and the other of A and B is substituted with neithera polar nor a nonpolar group, or (iii) one of A or B is substituted witha polar (P) group and the other of A or B is substituted with a nonpolar(NP) group; or, one of A and B is o-, m-, p-phenylene orheteroarylene—the other of A and B is a C₃ to C₈ cycloalkyl or (CH₂)_(q)where q is 1 to 7 wherein (i) one of A or B is optionally substituted byone or more polar (P) group(s) and the other of A or B is optionallysubstituted with one or more nonpolar (NP) group(s), or (ii) A issubstituted with a polar (P) group and a nonpolar (NP) group and B is aC₃ to C₈ cycloalkyl or (CH₂)_(q) where q is 1 to 7 and B is optionallyindependently substituted with one or more polar (P) or nonpolar (NP)group;

[0064] R¹ is (i) -y-C and R² is OH or NH₂ wherein C is selected from agroup consisting of C₁-C₆ allcyl, vinyl, 2-propenyl, H-x-(CH₂)_(p)—,(C₁-C₆-alkoxy)C(═O)(CH₂)_(p)—, C₁-C₆ alkoxy, benzyloxy, t-butoxy,pyridine and phenyl said pyridine or phenyl optionally substituted with1 or 2 substituents independently selected from a group consisting ofhalo, nitro, cyano, C₁-C₆ alkoxy, C₁-C₆ alkoxycarbonyl, andbenzyloxycarbonyl; or, (ii) is H and R² is -x-(CH₂)_(p)—W wherein x isas defined above and p is as defined below and W is N-maleimide or V asdefined below, or (iii) R₁ and R₂ together are a single bond;

[0065] NP is a nonpolar group an independently selected from R⁴ or—U—(CH₂)_(p)—R⁴ wherein R⁴ is selected from a group consisting ofhydrogen, C₁-C₁₀ alkyl, C₃-C₁₈ branched alkyl, C₃-C₈ cycloalkyl,monocyclic or polycyclic phenyl optionally substituted with one or moreC₁-C₄ alkyl, C₁-C₄ alkoxy or halo groups and monocyclic or polycyclicheteroaryl optionally substituted with one or more C₁-C₄ alkyl, C₁-C₄alkoxy, or halo groups and U and p are as defined below;

[0066] P is a polar group selected from a group consisting of IIIa,hydroxyethoxymethyl, methoxyethoxymethyl and polyoxyethylene

—U—(CH₂)_(p)—V  (IIIa)

[0067] wherein,

[0068] U is absent or selected from a group consisting of O, S, S(═O),S(═O)₂, NH, —C(═O)O—, —C(═O)NH—, —C(═O)S—, —C(═S)NH—, —S(═O)₂NH—, andC(═NO—) wherein groups with two chemically nonequivalent termini canadopt both possible orientations;

[0069] V is selected from a group consisting of amino, hydroxyl, thio,C₁-C₆ alkylamino, C₁-C₆ dialkylamino, NH(CH₂)_(p)NH₂, N(CH₂CH₂NH₂)₂,amidine, guanidine, semicarbazone, C₁-C₆ alkoxycarbonyl, basicheterocycle, and phenyl optionally substituted with an amino, C₁-C₆alkylamino, C₁-C₆ dialkylamino and lower acylamnino optionallysubstituted with one or more amino, lower alkylamino or lowerdialkylamino;

[0070] and the alkylene chain is optionally substituted with an amino orhydroxyl group or unsaturated;

[0071] p is independently 0 to 8;

[0072] m is 2 to at least about 500.

[0073] Another embodiment of polymer compound of formula VII:

[0074] wherein

[0075] one of R⁹ or R¹⁰ and R¹¹ is a polar (P) group and the other of R⁹or R¹⁰ and R¹¹ is a nonpolar (NP) group;

[0076] P is a polar group selected from a group consisting of IIIb,hydroxyethoxymethyl, methoxyethoxymethyl or polyoxyethylene

—(CH₂)_(p)—V  (IIIb)

[0077] wherein:

[0078] V is selected from a group consisting of amino, hydroxyl, C₁-C₆allcylamino, C₁-C₆ dialkylamino, NH(CH₂)_(p)NH₂, N(CH₂CH₂NH₂)₂, amidine,guanidine, semicarbazone, imidazole, piperidine, piperazine,4-alkylpiperazine and phenyl optionally substituted with an amino, C₁-C₆alkylamino, C₁-C₆ dialkylamino and lower acylamino optionallysubstituted with one or more amino, lower alkylamino or lowerdialkylamino; and,

[0079] the alkylene chain is optionally substituted with an amino orhydroxyl group;

[0080] p is independently 0 to 8; and,

[0081] m is 2 to at least about 30.

[0082] Still another embodiment of the present invention is a polyrnericcompound of formula IX

[0083] wherein:

[0084] one of R⁹ or R¹¹ is either a polar (P) group or a nonpolar (NP)group and the other of R⁹ or R¹¹ is the other of a polar (P) group or anonpolar (NP) group;

[0085] NP is —(CH₂)_(p)—R⁴ wherein R⁴ is selected from a groupconsisting of hydrogen, C₁-C₄ alkyl, C₃-C₁₂ branched alkyl, C₃-C₈cycloalkyl, phenyl optionally substituted with one or more C₁-C₄ alkylgroups C₁-C₄ alkoxy or halo groups and heteroaryl optionally substitutedwith one or more C₁-C₄ alkyl group, C₁-C₄ alkoxy or halo groups and p isas defined below;

[0086] P is a polar group selected from a group consisting of IIIb,hydroxyethoxymethyl, methoxyethoxymethyl or polyoxyethylene

—(CH₂)_(p)—V  (IIIb)

[0087] wherein:

[0088] V is selected from a group consisting of amino, hydroxyl, C₁-C₆alkylamino, C₁-C₆ dialkylamino, NH(CH₂)_(p)NH₂, N(CH₂CH₂NH₂)₂, amidine,guanidine, semicarbazone, imidazole, piperidine, piperazine,4-alkylpiperazine and phenyl optionally substituted with an amino, C₁-C₆alkylamino, C₁-C₆ dialkylamino and lower acylamino optionallysubstituted with one or more amino, lower alkylamino or lowerdialkylamino; and,

[0089] the alkylene chain is optionally substituted with an amino orhydroxyl group.

[0090] p is independently 0 to 8.

[0091] An embodiment of the present invention is a polymeric compound offormula IX wherein R⁹ is a polar side chain of a natural amino acids andR¹¹ is selected from a group consisting of methyl, ethyl, n-propyl,iso-propyl, n-butyl iso-butyl, sec-butyl, tert-butyl, n-pentyl,iso-pentyl, sec-pentyl, and benzyl.

[0092] Another embodiment of the present invention is polymeric compoundof formula IX wherein R⁹ is a nonpolar side chain of a natural aminoacids and R¹¹ is a polar group selected from a group consisting of IIIb,hydroxyethoxymethyl, methoxyethoxymethyl or polyoxyethylene

—(CH₂)_(p)—V  (IIIb)

[0093] wherein:

[0094] V is selected from a group consisting of amino, hydroxyl, C₁-C₆alkylamino, C₁-C₆ dialkylamino, NH(CH₂)_(p)NH₂, N(CH₂CH₂NH₂)₂, amidine,guanidine, semicarbazone, imidazole, piperidine, piperazine,4-alkylpiperazine and phenyl optionally substituted with an amino, C₁-C₆alkylamino, C₁-C₆ dialkylamino and lower acylamino optionallysubstituted with one or more amino, lower alkylamino or lowerdialkylamino; and,

[0095] p is independently 0 to 8.

[0096] Still another embodiment of the present invention is a polymericcompound of formula I wherein:

[0097] x is NH and y is C═O or C═S;

[0098] A and B are independently optionally substituted o-, m-, orp-phenylene, 2,5-thiophenylene or 2,5-pyrrolene;

[0099] NP is a nonpolar group independently selected from R⁴ or—U—(CH₂)_(p)—R⁴ wherein R⁴ is selected from a group consisting ofhydrogen, C₁-C₄ alkyl, C₃-C₁₂ branched alkyl, C₃-C₈ cycloalkyl, phenyloptionally substituted with one or more C₁-C₄ alkyl groups C₁-C₄ alkoxyor halo groups and heteroaryl optionally substituted with one or moreC₁-C₄ alkyl group, C₁-C₄ alkoxy or halo groups and U and p are asdefined below;

[0100] P is a polar group selected from a group consisting of IIIa,hydroxyethoxymethyl, methoxyethoxymethyl or polyoxyethylene

—U—(CH₂)_(p)—V  (IIIa)

[0101] wherein:

[0102] U is absent, O, S, SO, SO₂, or NH;

[0103] V is selected from a group consisting of amino, hydroxyl, C₁-C₆alkylamino, C₁-C₆ dialkylamino, NH(CH₂)_(p)NH₂, N(CH₂CH₂NH₂)₂, amidine,guanidine, semicarbazone, imidazole, piperidine, piperazine,4-alkylpiperazine and phenyl optionally substituted with an amino, C₁-C₆alkylamino, C₁-C₆ dialkylamino and lower acylamino optionallysubstituted with one or more amino, lower alkylamino or lowerdialkylamino; and,

[0104] the alkylene chain is optionally substituted with an amino orhydroxyl group;

[0105] p is independently 0 to 8;and,

[0106] m is 2 to at least about 500.

[0107] An embodiment of the present invention is a polymeric compound offormula I wherein:

[0108] x is NR³, R³ is hydrogen, and y is C═O or C═S;

[0109] A and B are independently optionally substituted o-, m-, orp-phenylene;

[0110] NP is a nonpolar group independently selected from R⁴ or—U—(CH₂)_(p)—R⁴ wherein R⁴ is selected from a group consisting ofhydrogen, methyl, ethyl, n-propyl, iso-propyl, n-butyl, iso-butyl,sec-butyl, tert-butyl, n-pentyl, iso-pentyl, and sec-pentyl and U and pare as defined below;

[0111] P is a polar group U—(CH₂)_(p)—V wherein U is absent or selectedfrom a group consisting of O and S, and V is selected from a groupconsisting of amino, lower alkyl amino, lower dialkylamino, imidazole,guanidine, NH(CH₂)_(p)NH₂, N(CH₂CH₂NH₂)₂, pyridine, piperidine,piperazine, 4-alkylpiperazine; and

[0112] p is independently 0 to 8;

[0113] m is 2 to at least about 500.

[0114] Another embodiment of the present invention is a polymericcompound of formula I wherein:

[0115] x is NR³, y is CO, and R³ is hydrogen;

[0116] A and B are m- or p-phenylene wherein (i) A is substituted at the2-position with a polar (P) group and B is substituted at the 5-positionwith a nonpolar (NP) group, (ii) A is substituted at the 2-position witha polar (P) group and at the 5-position with a nonpolar (NP) group and Bis substituted at the 2-position with a nonpolar (NP) group and at the5-position with a polar (P) group or, (iii) A is substituted at the2-position with one of a polar (P) or nonpolar (NP) group and B issubstituted at the 2-position with the other of a nonpolar (NP) or apolar (P) group;

[0117] NP is a nonpolar group independently selected from R⁴ or —U—R⁴wherein R⁴ is selected from a group consisting of methyl, ethyl,n-propyl, iso-propyl, n-butyl, iso-butyl, sec-butyl, tert-butyl,n-pentyl, iso-pentyl, and sec-pentyl and U and p are as defined below;

[0118] p is independently 0 to 8; and,

[0119] m is 2 to at least about 500.

[0120] Still another embodiment of the present invention is a polymericcompound of formula XII

[0121] wherein:

[0122] NP is a nonpolar group independently selected from a groupconsisting of methyl, ethyl, n-propyl, iso-propyl, n-butyl, iso-butyl,sec-butyl, tert-butyl, n-pentyl, iso-pentyl, and sec-pentyl and U and pare as defined below;

[0123] P is a polar group U—(CH₂)_(p)—V wherein U is selected from agroup consisting of O, S, or no atom and V is selected from a groupconsisting of amino, lower alkyl amino, lower dialkylamino, imidazole,guanidine, NH(CH₂)_(p)NH₂, and N(CH₂CH₂NH₂)₂, piperidine, piperazine,4-alkylpiperazine; and,

[0124] p is independently 0 to 8;

[0125] m is 2 to at least about 30.

[0126] Yet another embodiment of the present invention is a polymeraccording to claim 8 comprising a compound of formula XIV,

[0127] wherein:

[0128] NP is a nonpolar group independently selected from R⁴ or —U—R⁴wherein R⁴ is selected from a group consisting of methyl, ethyl,n-propyl, iso-propyl, 12-butyl, iso-butyl, sec-butyl, tert-butyl,n-pentyl, iso-pentyl, and sec-pentyl and U and p are as defined below;

[0129] P is a polar group U—(CH₂)_(p)—V wherein U is selected from agroup consisting of O, S, or no atom and V is selected from a groupconsisting of amino, lower alkyl amino, lower dialkylamino, imidazole,guanidine, NH(CH₂)_(p)NH₂, and N(CH₂CH₂NH₂)₂, piperidine, piperazine,4-alkylpiperazine; and,

[0130] p is independently 0 to 8;

[0131] m is 2 to at least about 30.

[0132] Yet another embodiment of the present invention is a polymericcompound of formula I wherein:

[0133] x is NR³, y is CO, and R³ is hydrogen;

[0134] A and B are o-phenylene wherein A is substituted at the5-position with a polar (P) group and B is substituted at the 5-positionwith a nonpolar (NP) group;

[0135] NP is a nonpolar group independently selected from R⁴ or —U—R⁴wherein R⁴ is selected from a group consisting of methyl, ethyl,n-propyl, iso-propyl, iso-butyl, n-butyl, sec-butyl, tert-butyl,n-pentyl, iso-pentyl, and sec-pentyl and U and p are as defined below;

[0136] P is a polar group U—(CH₂)_(p)—V wherein U is selected from agroup consisting of O, S, or no atom and V is selected from a groupconsisting of amino, lower alkyl amino, lower dialkylamino, imidazole,guanidine, NH(CH₂)_(p)NH₂, and N(CH₂CH₂NH₂)₂, pyridine, piperidine,piperazine, 4-alkylpiperazine;

[0137] p is independently 0 to 8; and,

[0138] m is 2 to at least about 500.

[0139] Another embodiment of the present invention is a polymericcompound of formula XIII:

[0140] wherein:

[0141] NP is a nonpolar group independently selected from a the groupconsisting of methyl, ethyl, n-propyl, iso-propyl, n-butyl, iso-butyl,sec-butyl, tert-butyl, n-pentyl, iso-pentyl, and sec-pentyl and U and pare as defined below;

[0142] P is a polar group (CH₂)_(p)—V wherein V is selected from a groupconsisting of amino, lower alkyl amino, lower dialkylamino, guanidine,piperazine, 4-alkylpiperazine;

[0143] p is independently 0 to 8;

[0144] m is 2 to at least about 30.

[0145] An embodiment of the present invention is a polymeric compound offormula XV:

[0146] wherein

[0147] either R¹² and R¹⁴ are independently polar (P) groups and R¹³ andR¹⁵ are independently nonpolar (NP) groups substituted at one of theremaining unsubstituted carbon atoms, or R¹² and R¹⁴ are independentlynonpolar (NP) groups and R¹³ and R¹⁵ are independently polar (P) groups

[0148] NP is a nonpolar group independently selected from R⁴ or —U—R⁴wherein R⁴ is selected from a the group consisting of methyl, ethyl,n-propyl, iso-propyl, n-butyl, iso-butyl, sec-butyl, tert-butyl,n-pentyl, iso-pentyl, and sec-pentyl and U is defined below;

[0149] P is a polar group U—(CH₂)_(p)—V wherein U is selected from agroup consisting of O or S and V is selected from a group consisting ofamino, lower alkyl amino, lower dialkylamino, guanidine, pyridine,piperazine, 4-alkylpiperazine;

[0150] p is independently 0 to 8;

[0151] m is 2 to at least about 30.

[0152] An embodiment of the present invention is a polymeric compound offormula II wherein:

[0153] x and y can be (i) taken independently wherein x is NR³, O, S,(CR⁷R⁸)NR³, (CR⁷R⁸), or (CR⁷R⁸)S, y is C═O, C═S, O═S═O, —C(═O)C(═O)—,(CR⁵R⁶)C═O or (CR⁵R⁶)C═S, and R³ is hydrogen, methyl or ethyl; or, (ii)taken together to be pyromellitic diimide; and R⁵ and R⁶ together are(CH₂)₂NR¹²(CH₂)₂ and R¹² is selected from a group consisting of hydrogen—C(═N)CH₃ or C(═NH)—NH₂; and R⁷ and R⁸ together are (CH₂)_(p) wherein pis as defined below;

[0154] both A and B are independently optionally substituted o-, m-,p-phenylene, or optionally substituted heteroarylene wherein (i) A and Bare both substituted with a polar (P) group and a nonpolar (NP) group,(ii) one of A and B is substituted with a polar (P) group and a nonpolar(NP) group and the other of A and B is substituted with neither a polarnor a nonpolar group, or (iii) one of A or B is substituted with a polar(P) group and the other of A or B is substituted with a nonpolar (NP)group;

[0155] R¹ is (i) —B-y-R² and R² is -x-(CH₂)_(p)—W wherein x is asdefined above and W is hydrogen, phenyl optionally substituted with upto three substituents selected from a group consisting of halogen, C₁-C₄alkyl, C₁-C₄ alkoxy, and carboxyl, N-maleimide, or V as defined below,and p is an defined below; or, (ii) R¹ and R² together are a single bond

[0156] NP is a nonpolar group an independently selected from R⁴ or—U—(CH₂)_(p)—R⁴ wherein R⁴ is selected from a group consisting ofhydrogen, C₁-C₁₀ alkyl, C₃-C₁₈ branched alkyl, C₃-C₈ cycloalkyl,monocyclic or polycyclic phenyl optionally substituted with one or moreC₁-C₄ alkyl, C₁-C₄ alkoxy or halo groups and monocyclic or polycyclicheteroaryl optionally substituted with one or more C₁-C₄ alkyl, C₁-C₄alkoxy, or halo groups and U and p are as defined below;

[0157] P is a polar group selected from a group consisting of IIIa,hydroxyethoxymethyl, methoxyethoxymethyl and polyoxyethylene

—U—(CH₂)_(p)—V  (IIIa)

[0158] wherein,

[0159] U is absent or selected from a group consisting of O, S, S(═O),S(═O)₂, NH, —C(═O)O—, —C(═O)NH—, —C(═O)S—, —C(═S)NH—, —S(═O)₂NH—, andC(═NO—) wherein groups with two chemically nonequivalent termini canadopt both possible orientations;

[0160] V is selected from a group consisting of amino, hydroxyl, thio,C₁-C₆ alkylamino, C₁-C₆ dialkylamino, NH(CH₂)_(p)NH₂, N(CH₂CH₂NH₂)₂,amidine, guanidine, semicarbazone, C₁-C₆ alkoxycarbonyl, basicheterocycle, and phenyl optionally substituted with an amino, C₁-C₆alkylamino, C₁-C₆ dialkylamino and lower acylamino optionallysubstituted with one or more amino, lower alkylamino or lowerdialkylamino;

[0161] and the alkylene chain is optionally substituted with an amino orhydroxyl group or unsaturated;

[0162] p is independently 0 to 8;

[0163] m is 2 to at least about 500.

[0164] Another embodiment of the present invention is a polymericcompound of formula II wherein:

[0165] x=NH and y=CO;

[0166] A and B are m- or p-phenylene wherein (i) A is substituted at the2-position with a polar (P) group and B is substituted at the 5-positionwith a nonpolar (NP) group, or (ii) A is substituted at the 2-positionwith a polar (P) group and at the 5-position with a nonpolar (NP) groupand B is either substituted at the 2-position with a nonpolar (NP) groupand at the 5-position with a polar (P) group or B is unsubstituted;

[0167] NP is a nonpolar group independently selected from R⁴ or—U—(CH₂)_(p)—R⁴ wherein R⁴ is selected from a group consisting ofmethyl, ethyl, n-propyl, iso-propyl, iso-butyl, sec-butyl, tert-butyl,iso-pentyl, and sec-pentyl and U and p are as defined below;

[0168] P is a polar group U—(CH₂)_(p)—V wherein U is absent or selectedfrom a group consisting of O and S, and V is selected from a groupconsisting of amino, lower alkyl amino, lower dialkylamino, imidazole,guanidine, NH(CH₂)_(p)NH₂, N(CH₂CH₂NH₂)₂, piperidine, 4-alkylpiperazineand;

[0169] p is independentlyo to 8;

[0170] m is 2 to at least about 500.

[0171] Yet another embodiment of the present invention is a polymericcompound of formula II where A is an optionally substituted1,3-diaminobenzene and B is an optionally substituted iso-phthalic acid.

[0172] Still another embodiment of the present invention is a polymericcompound of formula XI

[0173] wherein:

[0174] R⁴ is selected from a group consisting of methyl, ethyl,n-propyl, iso-propyl, n-butyl, iso-butyl, sec-butyl, tert-butyl,ii-pentyl, iso-pentyl, and sec-pentyl;

[0175] U is O or S;

[0176] V is amino, lower alkyl amino, lower dialkylamino, guanidine;

[0177] p is independently 0-8;

[0178] m is 2 to at least about 30.

[0179] Another embodiment of the present invention is a polymericcompound of formula XVI

[0180] wherein:

[0181] either R¹² and R¹⁴ are independently polar (P) groups and R¹³ andR¹⁵ are independently nonpolar (NP) groups substituted at one of theremaining unsubstituted carbon atoms, or R¹² and R¹⁴ are independentlynonpolar (NP) groups and R¹³ and R¹⁵ are independently polar (P) groups

[0182] NP is a nonpolar group independently selected from R⁴ or —U—R⁴where R⁴ is selected from a group consisting of methyl, ethyl, n-propyl,iso-propyl, n-butyl, iso-butyl, sec-butyl, tert-butyl, n-pentyl,iso-pentyl, and sec-pentyl, and U is as defined below;

[0183] P is a polar group U—(CH₂)_(p)—V wherein U is absent or selectedfrom a group consisting of O and S, and V is selected from a groupconsisting of amino, lower alkyl amino, lower dialkylamino, imidazole,guanidine, NH(CH₂)_(p)NH₂, N(CH₂CH₂NH₂)₂, piperidine, and4-alkylpiperazine;

[0184] U is O or S;

[0185] V is amino, lower alkyl amino, lower dialkylamino, guanidine;

[0186] p is independently 0 to 8; and

[0187] m is 2 to at least about 30.

[0188] Still another embodiment of the present invention is a polymericcompound of formula XX

[0189] wherein j is independently 0 or 1, R⁵ and R⁶ together are(CH₂)₂NH(CH₂)₂ and R⁷ and R⁸ together are (CH₂)_(p) wherein p is 4 to 6

[0190] Yet another embodiment of the present invention is a polymericcompound of formula IV

[0191] wherein:

[0192] x is NR³ or NHNH and y is NR³, NHNH, S or O, and R³ is hydrogen,methyl or ethyl;

[0193] z is C═O, —(C═O)C(═O)—, C═S or O═S═O;

[0194] A and B are independently optionally substituted o-, m-,p-phenylene or optionally substituted heteroarylene wherein (i) A and Bare both substituted with a polar (P) group and a nonpolar (NP) group(NP), (ii) one of A and B is substituted with a polar (P) group and anonpolar (NP) group and the other of A and B is substituted with neithera polar nor a nonpolar group, or (iii) one of A or B is substituted withone or two polar (P) group(s) and the other of A or B is substitutedwith one or two nonpolar (NP) group(s), or, or (iv) A is substituted atthe 2-position with a polar (P) group and at the 5-position with anonpolar (NP) group and B is unsubstituted;

[0195] R¹ is (i) —B-y-R² and R² is -x-(CH₂)_(p)—W wherein x is asdefined above and W is hydrogen, pyridine and phenyl said pyridine orphenyl optionally substituted with 1 or 2 substituents independentlyselected from a group consisting of halo, nitro, cyano, C₁-C₆ alkoxy,C₁-C₆ alkoxycarbonyl, and benzyloxycarbonyl; R¹ is H and R² is-x-(CH₂)_(p)—V or (ii) R₁ and R₂ together are a single bond;

[0196] NP is a nonpolar group independently selected from R⁴ or—U—(CH₂)_(p)—R⁴ wherein R⁴ is selected from a group consisting of C₁-C₁₈alkyl, C₃-C₁₈ branched alkyl, C₃-C₈ cycloalkyl, monocyclic or polycyclicphenyl optionally substituted with one or more C₁-C₄ alkyl or halogroups, and monocyclic or polycyclic heteroaryl optionally substitutedwith one or more C₁-C₄ alkyl or halo groups and U and p are as definedbelow;

[0197] P is a polar group selected from a group consisting of IIIa,hydroxyethoxymethyl, methoxyethoxymethyl and polyoxyethylene

—U—(CH₂)_(p)—V  (IIIa)

[0198] wherein;

[0199] U is absent or selected from a group consisting of O, S, S(═O),S(═O)₂, NH, —C(═O)O—, —C(═O)NH—, —C(═O)S—, —C(═S)NH—, —S(═O)₂NH—, andC(═NO—) wherein groups with two chemically nonequivalent termini canadopt both possible orientations;

[0200] V is selected from a group consisting of amino, hydroxyl, C₁-C₆alkylamino, C₁-C₆ dialkylamino, NH(CH₂)_(p)NH₂, N(CH₂CH₂NH₂)₂, amidine,guanidine, semicarbazone, basic heterocycle, and phenyl optionallysubstituted with an amino, C₁-C₆ alkylamino, C₁-C₆ dialkylamino andlower acylamino optionally substituted with one or more amino, loweralkylamino or lower dialkylamino;

[0201] and the alkylene chain is optionally substituted with an amino orhydroxyl group or optionally unsaturated;

[0202] p is independently 0 to 8;

[0203] m is 2 to at least about 500.

[0204] Yet another embodiment of the present invention is a polymericcompound of formula IV wherein:

[0205] x and y are NR³, z is C═O or C═S, and R³ is hydrogen;

[0206] A and B are independently optionally substituted o-, m-, orp-phenylene;

[0207] NP is a nonpolar group independently selected from R⁴ or—U—(CH₂)_(p)—R⁴ wherein R⁴ is selected from a group consisting ofhydrogen, C₁-C₄ alkyl, C₃-C₁₂ branched alkyl, C₃-C₈ cycloalkyl, phenyloptionally substituted with one or more C₁-C₄ alkyl groups andheteroaryl optionally substituted with one or more C₁-C₄ alkyl groupsand U and p are as defined below;

[0208] P is a polar group selected from consisting of IIIa,hydroxyethoxymethyl, methoxyethoxymethyl or polyoxyethylene

—U—(CH₂)_(p)—V  (IIIa)

[0209] wherein

[0210] U is O, S, S(═O), S(═O)₂, NH, or absent;

[0211] V is selected from a group consisting of amino, hydroxyl, C₁-C₆alkylamino, C₁-C₆ dialkylamino, NH(CH₂)_(p)NH₂, N(CH₂CH₂NH₂)₂, amidine,guanidine, semicarbazone, and imidazole, piperidine, piperazine,4-alkylpiperazine and phenyl optionally substituted with an amino, C₁-C₆alkylamino, C₁-C₆ dialkylamino and lower acylamino optionallysubstituted with one or more amino, lower alkylamino or lowerdialkcylamino;

[0212] and the alkylene chain is optionally substituted with an amino orhydroxyl group;

[0213] p is independently 0 to 8; and,

[0214] m is 2 to at least about 500.

[0215] An embodiment of the present invention is a polymeric compound offormula IV wherein:

[0216] x and y are NH, z is C═O;

[0217] A and B are m- or p-phenylene and either (i) A is substituted atthe 2-position with a polar (P) group and B is substituted at the5-position with a nonpolar (NP) group, or (ii) A is substituted at the5-position with a polar (P) group and B is substituted at the 2-positionwith a nonpolar (NP) group, or (iii) A and B are both substituted at the2-position with a polar (P) group and at the 5-position with a nonpolar(NP) group, or (iv) A is substituted at the 2-position with a polar (P)group and at the 5-position with a nonpolar (NP) group and B isunsubstituted;

[0218] NP is a nonpolar group independently selected from R⁴ or—U—(CH₂)_(p)—R⁴ wherein R⁴ is selected from a group consisting ofhydrogen, methyl, ethyl, n-propyl, iso-propyl, iso-butyl, sec-butyl,tert-butyl, iso-pentyl, and sec-pentyl and U and p are as defined below;

[0219] P is a polar group U—(CH₂)_(p)—V wherein U is absent or selectedfrom a group consisting of O, S and V is selected from a groupconsisting of amino, lower alkyl amino, lower dialkylamino, imidazole,guanidine, NH(CH₂)_(p)NH₂, and N(CH₂CH₂NH₂)₂, piperidine, piperazine,4-alkylpiperazine;

[0220] p is independently 0 to 8; and,

[0221] m is 2 to at least about 500.

[0222] Another embodiment of the present invention is a polymericcompound of formula XIV

[0223] R⁴ is selected from a group consisting of methyl, ethyl,n-propyl, iso-propyl, n-butyl, iso-butyl, sec-butyl, tert-butyl,n-pentyl, iso-pentyl, and sec-pentyl and U and p are as defined below;

[0224] U is absent, O or S and V is selected from a group consisting ofamino, lower alkyl amino, lower dialkylamino, imidazole, guanidine,NH(CH₂)_(p)NH₂, and N(CH₂CH₂NH₂)₂, piperidine, piperazine,4-alkylpiperazine; and,

[0225] p is 0 to 8;

[0226] m is 2 to at least about 30.

[0227] Still another embodiment of the present invention is a polymericcompound of formula XVII

[0228] wherein:

[0229] either R¹² and R¹⁴ are independently polar (P) groups and R¹³ andR¹⁵ are independently nonpolar (NP) groups substituted at one of theremaining unsubstituted carbon atoms, or R¹² and R¹⁴ are independentlynonpolar (NP) groups and R¹³ and R¹⁵ are independently polar (P) groups

[0230] NP is a nonpolar group independently selected from R⁴ or —U—R⁴wherein R⁴ is selected from a the group consisting of methyl, ethyl,n-propyl, iso-propyl, n-butyl, iso-butyl, sec-butyl, tert-butyl,n-pentyl, iso-pentyl, and sec-pentyl and U and p are as defined below;

[0231] P is a polar group U—(CH₂)_(p)—V wherein U is selected from agroup consisting of O or S and V is selected from a group consisting ofamino, lower alkyl amino, lower dialkylamino, guanidine, pyridine,piperazine, 4-alkylpiperazine;

[0232] p is independently 0 to 8; and,

[0233] m is 2 to at least about 30.

[0234] Another embodiment of the present invention is a polymericcompound of formula XVIII

[0235] wherein:

[0236] NP is a nonpolar group independently selected from R⁴ or—(CH₂)_(p)—R⁴ wherein R⁴ is selected from a group consisting of hydrogenmethyl, ethyl, n-propyl, iso-propyl, n-butyl, iso-butyl, sec-butyl,tert-butyl, n-pentyl, iso-pentyl, and sec-pentyl and p is as definedbelow;

[0237] P is a polar group (CH₂)_(p)—V wherein V is selected from a groupconsisting of amino, lower alkyl amino, lower dialkylamino, imidazole,guanidine, NH(CH₂)_(p)NH₂, and N(CH₂CH₂NH₂)₂, piperidine, piperazine,4-alkylpiperazine;

[0238] p is independently 0 to 8; and,

[0239] m is 2 to at least about 30.

[0240] Polyamides and polyesters that are useful for the presentinvention can be prepared by typical condensation polymerization andaddition polymerization processes. [G. Odian, Principles ofPolymerization, John Wiley & Sons, Third Edition (1991), M. Steven,Polymer Chemistry, Oxford University Press, (1999)] Most commonly thepolyamides are prepared by (a) thermal dehydration of amine salts ofcarboxylic acids, (b) reaction of acid chlorides with amines and (c)aminolysis of esters. Methods (a) and (c) are of limited use inpolymerizations of aniline derivatives which are generally preparedutilizing acid chlorides. The skilled chemist, however, will recognizethat there are many alternative active acylating agents, for examplephosphoryl anhydrides, active esters or azides, which may replace anacid chloride and which, depending of the particular polymer beingprepared, may be superior to an acid chloride. The acid chloride routeis probably the most versatile and has been used extensively for thesynthesis of aromatic polyamides

[0241] Homopolymers derived from substituted aminobenzoic acidderivatives (FIG. 1) can also prepared in a stepwise fashion. A stepwiseprocess comprises coupling an N-protected amino acid to an amine (orhydroxy group) and subsequently removing the amine-protecting group andrepeating the process. These techniques have been highly refined forsynthesis of specific peptides, allow for the synthesis of specificsequences, and both solid-phase and solution techniques for peptidesynthesis are directly applicable to the present invention. Analternative embodiment of the present invention is the correspondingpolysulfonamides that can be prepared in analogous fashion bysubstituting sulfonyl chlorides for carboxylic acid chlorides.

[0242] The most common method for the preparation of polyureas is thereaction of diamines with diisocyanates. (Yamaguchi, I. et al. Polym.Bull. 2000 44, 247) This exothermic reaction can be carried out bysolution techniques or by interfacial techniques. One skilled in organicand polymer chemistry will appreciate that the diisocyanate can bereplaced with a variety of other bis-acylating agents e.g., phosgene orN, N′-(diimidazolyl)carbonyl, with similar results. Polyurethanes areprepared by comparable techniques using a diisocyanate and a dialcoholor by reaction of a diamine with a bis-chloroformate.

[0243] The syntheses of appropriately substituted monomers arestraightforward. Numerous pathways are available to incorporate of polarand nonpolar side chains. Phenolic groups on the monomer can bealkylated. Alkylation of the commercially available phenol will beaccomplished with standard Williamson ether synthesis for the non-polarside chain with ethyl bromide as the alkylating agent. Polar sidechainscan be introduced with bifunctional alkylating agents such asBOC-NH(CH₂)₂Br. Alternatively the phenol group can be alkylated toinstall the desired polar side chain function by employing Mitsonobureaction with BOC-NH(CH₂)₂—OH, triphenyl phosphine, and diethylacetylenedicarboxylate, Standard conditions for reduction of the nitrogroups and hydrolysis of the ester afford the amino acid. With theaniline and benzoic acid in hand coupling can be effected under avariety of conditions. Alternatively the hydroxy group of the(di)nitrophenol can be converted to a leaving group and functionalityintroduced under nucleophilic aromatic substitution conditions (FIG. 8).Other potential scaffolds that can be prepare with similar sequences aremethyl 2-nitro-4-hydroxybenzoate (FIG. 9) and methyl 2-hydroxy-4-nitrobenzoate.

[0244] Antimicrobial testing is carried out using the micro-brothdilution technique with E. coli. Other organisms screened includeampicillin & streptomycin-resistant E. coli D31, B. subtilis,vancomycin-resistant Enterococcus faecium A436, andmethicillin-resistant S. aureus 5332. Any peptide that is found to beactive will be purified to homogeneity, and retested to obtain anaccurate IC₅₀. Secondary screens include Klebsiella pneumoniae Kp1, andSalmonella typhimunium S5, and Pseudomonus aeruginosa 10. Traditionally,the micro-broth dilution technique only evaluates a single data pointbetween 18-24 hours; however, the measurements can be extended to 24 hrto monitor cell growth through the entire growth phase. Theseexperiments are performed in LB medium (which is a rich medium typicallyused to grow cells for protein expression) and represent a criticalinitial screen for activity. Since salt concentrations, proteins, andother solutes can affect the activities of antibiotics, materials thatshowed no activity in rich medium were retested in minimal medium (M9)to determine if rich medium was limiting activity. No relationshipbetween the media and the activity was observed which is consistent withthe mode of action is believed to be through general membrane disruption

[0245] To determine the toxicity to mammalian, as well to bacterial,cells the biocidal activity is evaluated using both cultured cells andfreshly obtained human blood cells. Increasing concentration of polymerwill be added to both confluent and non-confluent cultures of humanumbilical endothelial cells (HUVEC, Cambrex). Cell number, monolayerintegrity, and cell viability (measured as trypan blue exclusion) willbe evaluated as a function of time in culture.

[0246] While the synthesis of a variety of polymer backbones is wellunderstood, computer-aided computational techniques can provide valuableinsight and guidance in the selection of potential antimicrobialpolymers. The goal of these computations is to identify potential lowenergy conformations which have a geometrical repeat that matches aconvenient sequence repeat of less than 6 monomer units. For example inα-amino acid oligomers, the geometrical repeat of the β-sheet is 2.0residues. Once these repeating scaffolds are identified and thefrequency of the repeat is calculated, polar and nonpolar substituentscan be incorporated into the monomers to confer amphiphilic propertiesinto the molecule.

[0247] High level ab initio calculations are one technique which willidentify accessible low energy conformations. Unfortunately, thesetechniques, while extremely powerful, are not practical with moleculesthe size of the present invention. Molecular Dynamics simulationsprovide an alternative that can be adapted efficiently to moleculesenvisioned in the present invention. Key elements in determiningconformational energies are strong electrostatic interactions (i.e.,intramolecular hydrogen bonding) between adjacent or more distantmonomers and rigidification caused by the backbone torsions or by bulkyfunctional groups. In order to simulate these interactions in molecularmechanics calculations the empirical parameters, i.e., a force field,must be determined for representative polymer backbones. Densityfunctional theory (DFT) can be used to carry out ab initio calculationson small model compounds that share the basic structural connectivity ofthe polymer backbones and which will generate required torsionalpotentials. The procedure to carry out these computations is:

[0248] 1. Select simple model compounds that share similar torsionalpatterns with the target polymer backbones.

[0249] 2. For each compound, perform a full geometric optimization atthe BLYP/6-31G(d) level of theory (multiple initial configurationsensure the global minimum is obtained).

[0250] 3. Calculate the single-point energy at the most stable geometryobtained in step 2 above, using B3LYP/6-311G++(dp) or plane wave CPMD.

[0251] 4. Constrain a relevant torsion to a set angle and repeat steps 2and 3.

[0252] 5. Repeat step 4 for several angles; the torsional energy isobtained by subtracting the non-bonded interactions.

[0253] 6. Fit energies versus torsion angle to a cosine series whosecoefficients are the force field parameters.

[0254] After verifying the suitability of the force field by comparingcomputed predictions of the structure and thermodynamic properties tomolecules that have similar torsional patterns and for whichexperimental data are available, the fitted torsions are then combinedwith bond stretching, bending, one-four, van der Waals, andelectrostatic potentials borrowed from the CHARMM (B. R. Brooks et al.J. Comp. Chem. 1983 4:187-217 and TraPPE (M. G. Martin and J. I.Siepmann, J. Phys. Chem B. 1999 103:4508-17; C. D. Wick et al. J. Phys.Chem B. 2000 104:3093-3104) molecular dynamics force fields. To identifyconformations that can adopt periodic folding patterns with polar groupsand apolar groups lined up on the opposite sides. Initial structures canbe obtained with the Gaussian package (M. Frisch et al. Gaussian 98(revision A.7) Gaussian Inc., Pittsburgh, Pa. 1998). Then, theparallelized plane-wave Car-Parrinello CP-MD (R, Car and M. ParrinelloPhys. Rev. Lett. 1985 55:2471-2474) program, (cf. U. Röthlisberger etal. J. Chem. Phys. 1996 3692-3700) is used to obtain energies at theminimum and constrained geometries. The conformations of the polymerswithout side-chains can be investigated in the gas phase. Both MD and MCmethods will be used to sample the conformations. The former is usefulfor global motions of the polymer. With biasing techniques (J. I.Siepmann and D. Frenkel Mol. Phys. 1992 75:59-70; M. G. Martin and J. I.Siepmann J. Phys. Chem. B 1999 103:4508-4517; T. J. H. Vlugt et al. Mol.Phys. 1998 94:727-733) the latter allows efficient sampling for polymerswith multiple local minimum configurations that are separated byrelatively large barriers.

[0255] The potential conformations are examined for positions to attachpendant groups that will impart amphiphilic character to the secondarystructure. Polymers selected from the gas-phase studies with suitablebackbone conformations and with side-chains at the optimal positions tointroduce amphiphilicity will be further evaluated in a modelinterfacial system, n-hexane/water, chosen because it is simple andcheap for calculations while it mimics well the lipid/water bilayerenvironment. Polymer secondary structures that require inter-polymerinteractions can be identified by repeating the above-mentionedcalculations using a periodically repeated series of unit cells ofvarious symmetries (so called variable cell molecular dynamics or MonteCarlo technique) with or without solvent. The results of thesecalculations will guide the selection of candidates for synthesis.

[0256] An embodiment of the present is a computation technique toidentify polymer backbones which can produce facially amphiphilicpolymers by:

[0257] (1) selecting a polymer backbones or scaffolds suitable forregiospecific introduction of polar (P) and nonpolar (NP) groups;

[0258] (2) determining parameters for a molecular mechanics force fieldutilizing ab initio quantum mechanical calculations;

[0259] (3) calculating energetically accessible conformations of saidbackbone using molecular dynamics or molecular mechanics calculations;

[0260] (4) identifying energetically accessible conformations of saidbackbone wherein the periodicity of a geometrical/conformational repeatmatches a sequence repeat;

[0261] (5) synthesizing monomers with polar and nonpolar substituents;

[0262] (6) synthesizing an antimicrobial polymer containing saidmonomers by solution or solid-phase synthesis.

[0263] The facially amphiphilic polymers of the present invention canhave a substantial range in molecular weight. Facially amphiphilicmolecules with molecular weights of about 0.8 kD to about 20 kD will bemore prone to leach from the surface of the substrate. The faciallyamphiphilic polymer may be attached to, applied on or incorporated intoalmost any substrate including but not limited to woods, paper,synthetic polymers (plastics), natural and synthetic fibers, natural andsynthetic rubbers, cloth, glasses and ceramics by appropriate methodsincluding covalent bonding, ionic interaction, coulombic interaction,hydrogen bonding or cross-linking. Examples of synthetic polymersinclude elastically deformable polymers which may be thermosetting orthermoplastic including, but not limited to polypropylene, polyethylene,polyvinyl chloride, polyethylene terephthalate, polyurethane,polyesters, such as polylactide, polyglycolide, rubbers such aspolyisoprene, polybutadiene or latex, polytetrafluoroethylene,polysulfone and polyethylenesulfone polymers or copolymers. Examples ofnatural fibers include cotton, wool and linen.

[0264] The polymers of the present invention thus provide asurface-mediated microbicide that only kills organisms in contact withthe surface. Moreover the polymers of the present invention are stableand retain their bioactivity for extended periods of time. Polymersbound to the surface will not leach out of the surface into theenvironment. Specificity can be imparted for microbial cell walls whichcan provide polymers with reduced toxicity to birds, fish, mammals andother higher organisms.

[0265] Any object that is exposed to or susceptible to bacterial ormicrobial contamination can be treated with these polymers. These needsare particularly acute in the health care and food industries. A growingconcern with preservatives has produced a need for new materials thatprevent microbiological contamination without including preservatives.The incidence of infection from food-borne pathogens is a continuingconcern and antimicrobial packaging material, utensils and surfaceswould be valuable. In the health care and medical device areas theutility of antimicrobial instruments, packaging and surfaces areobvious. Products used internally or externally in humans or animalhealth including, but not limited to, surgical gloves, implanteddevices, sutures, catheters, dialysis membranes, water filters andimplements, all can harbor and transmit pathogens. The polymers of thepresent invention can be incorporated into spinnable fibers for use inmaterials susceptible to bacterial contamination including fabrics,surgical gowns, and carpets. Ophthalmic solutions and contact lenseseasily become contaminated and cause ocular infections. Antimicrobialstorage containers for contact lens and cleaning solutions would be veryvaluable. Both pets and agronomic animals are exposed to and harbor avariety of infectious pathogenic organisms that can cause disease inanimals or humans.

[0266] Traditionally, monolayers have been created at air/waterinterfaces and transferred to a variety of surfaces for chemical andstructural characterization, as documented in a large body of workdating back to the seminal studies of Blodgett and Langmuir. Monolayerscan be chemically bonded to solid supports, resulting in stable,uniformly packed molecular layers that self-assemble by absorption.Typically, these Self-Assembled Monolayers (SAMS) are covalentlytethered to solids using either alkylsiloxane or thiolate-gold linkages(for reviews see M. Mrksich, Cell Mol Life Sci, 1998 54:653-62; M.Mrksich, and G. M. Whitesides Ann Rev Biophys Biomol Struct, 199625:55-78). Alkylthiolate-gold linkages can be formed on the surface ofgold by spontaneous absorption of a thiol or disulfide. Gold layers canbe deposited on most solid surfaces, providing great versatility.Alkylsiloxane monolayers can be prepared by reacting trialkoxysilanes ortrichlorosilanes with a silicon dioxide surface resulting in a monolayerof crosslinked siloxanes on the surface. Siloxane monolayers may beformed on any solid that contains surface silanol groups includingatomically smooth, surface-oxidized silicon wafers, glass and quartz.These two chemistries will allow amphiphilic polymers to be attached avariety of surfaces.

[0267] These amphiphilic polymers can incorporate linkers to allow thepolymers to more efficiently interact with the environment around thesolid surface. Tethering chemistries that allow presentation of peptidesand proteins in native conformations with minimal interaction with theunderlying substrate have been described. For examples, alkanethiols ofthe general form, HS—(CH₂)₁₁—(OCH₂—CH₂)_(n)—OH (denoted HS—C₁₁-E_(n),n=3-6), have now come into widespread use for studies of receptor/ligandinteractions (M. Mrksich Cell Mol. Life Sci. 1998 54:653-62; M. Mrksichand G. M. Whitesides Ann. Rev. Biophys. Biomol. Struct.1996 25:55-78).Polyethylene glycol derived amino acids, e.g.Fmoc-NH—(CH₂—CH₂—O)₂)CH₂—COOH (Neosystems) have also been described Cyswill be appended to the N-terminus to act as a group that allowscoupling via its thiol, directly or through chemoselective ligation (T.W. Muir et al. Methods Enzymol. 1997 289:266-98; G. G. Kochendoerfer etal. Biochemistry 1999 38:11905-13). The thiol group serves to tether themolecule to gold surfaces, while the terminal hydroxyl and ethyleneglycol groups project towards solvent, presenting a hydrophilic surface.Attachment to siloxane and polyethylene surfaces have also beendescribed. (S. P. Massia and J. Stark J. Biomned. Mat. res. 200156:390-9; S. P. Massia and J. A. Hubbell J. Cell Biol. 1991114:1089-1100; S. P. Massia and J. A. Hubbell Anal. Biochem. 1990187:292-301; B. T. Houseman and M. Mrksich Biomaterials 2001 22:943-55).

[0268] Resin bound intermediates can easily be modified to incorporatelinkers. Glass surfaces can be modified to allow reaction with the thiolgroups of the peptide by: (i) aminoalkylation of the glass surface bytreatment with trimethoxysilylpropylamine; (ii) reaction of the aminogroups with a bromoacetyl bromide or other heterobifunctionalcrosslinker groups capable of also reacting with a thiol group. In theabove example, we show an amino surface in which we have introducedbromoacetyl groups for subsequent reaction with peptide thiols.Alternatively, thiol-reactive maleimides, vinyl-sulfones (Michaelacceptors) may be incorporated using commercially availablecross-linking agents. Alternatively, the surface amino groups may beconverted to carboxylates by treatment with an anhydride, and thenconverted to thioesters under standard conditions. The resultingthioesters react facilely and with extreme regioselectivity with anN-terminal Cys residue. By incorporating quantities of inactive “filler”molecule, e.g. one example which is not limiting is a monofunctionalthiol-terminated short chain polyethylene glycol polymer with thereactive teathering group the molar ratio of the oligomer to the“filler” component, it should be possible to continuously vary thesurface density of the polymers attached to a solid support.

[0269] An embodiment of the present invention is a process for producingan antimicrobial surface by attaching a antimicrobial faciallyamphiphilic polymer to a surface comprising treating said surface with afirst chemically reactive group and reacting a facially amphiphilicpolymer linked to a second reactive group thereto.

[0270] Another embodiment of the present invention is a process forattaching a facially amphiphilic polymer to a surface wherein the solidsurface is treated with a 1-(trialkoxysilyl)alkylamine and faciallyamphiphilic polymer contains an activated carboxylic acid.

[0271] Yet another embodiment of the present invention is a process forattaching a facially amphiphilic polymer to a surface wherein the solidsurface is treated with a ω-(trialkoxysilyl)alkyl bromomethylacetamideand facially amphiphilic polymer contains a thiol.

[0272] Another embodiment of the present invention is a process forattaching a facially amphiphilic polymer to a surface wherein the solidsurface is treated with a N-[ω-(trialkoxysilyl)alkyl]maleimide andfacially amphiphilic polymer contains a thiol.

[0273] Still another embodiment of the present invention is a processfor attaching a facially amphiphilic polymer to a surface wherein thesurface is gold and the facially amphiphi;ic polymer contains a thiol.

[0274] A variety of polymers are used in a host of medical applicationswhich require sterile surfaces. Catheters, like venous or urinarycatheters are cause serious infections. Polyurethane based tubing is byfar the major source of commercial catheter tubing. Amphiphilic polymerscan be incorporated into polyurethane and other polymers using pre- andpost manufacture techniques. The advantage of pre-manufactureincorporation is simpler modification strategies and dispersion of theantimicrobial agent throughout the tubing materials. Tubingmanufacturing is typically an extrusion process in which pellets ofpolyurethane are heated and pressed through a dye producing tubing ofthe desired diameter. The thermal stability of urethane bonds is verysimilar to amide and urea bonds again suggesting that thermal processedconditions should not be a problem. For the pre-manufacture approach,designed antimicrobial polymers are added to the original polyurethanepellets before extrusion resulting in a uniform dispersion throughoutthe extruded polymer.

[0275] Post-manufacture modifications are also possible although in thiscase the antimicrobial polymer will only be present on the surface ofthe tubing. However, since catheters have a minimal life cycle it islikely that surface treatment will render the materials sufficientlysanitary for their application. There are a variety of methods one canuse to modify polymeric surfaces (E. Piskin J. Biomat. Sci.-Polymer Ed.1992 4:45-60). The most common technique to covalent attach aamphiphilic polymer to the surface relies on irradiation to produce freeradicals that form covalent bonds between the polymer and active surfaceagent. Unfortunately, this process is completely random with no controlover orientation or functional group attachment to the surface.Alternatively, photo or chemical oxidation of the polyurethane surfacecan create carboxylic acid or alcohol functionality which will bereactive toward these antimicrobial polymers (the cationic side chainsor cationic end groups). The most common technique for surface oxidationis plasma etching (E. Piskin loc. cit.; S. H. Hsu and W. C. Chen,Biomaterials 2000 21:359-67) although ozone can also be used. Afteroxidation, the surface is treated with a bifunctional epoxide followedby addition of the cationic antimicrobial polymer which can react withthe epoxide.

[0276] Microbial growth in paint and on the surface of paint films alsoremains an unsolved problem. This can occur in the wet formulated paintor by microbial growth on the dried surface. The paint industrycurrently uses either isothiazolones or “formaldehyde releasers” for wetpaint protection from microbes (G. Sekaran et al. J. Applied PolymerSci. 2001 81:1567-1571; T. J. Kelly et al. Environ. Sci. Technol. 199933:81-88; M. Sondossi et al. International Biodeterioration &Biodegradation 1993 32:243-61). Both of these products are harmful tohuman beings and great lengths and expense are taken at the factory tolimit employee exposure; however, there is no viable alternativecurrently for the industry. Isothiazolones are used mainly for theireffectiveness against Pseudomonas aeruginosa and that the antimicrobialpolymers discussed in preliminary data are active against this strain.

[0277] Any object that is exposed to or susceptible to bacterial ormicrobial contamination can be treated with these polymers. These needsare particularly acute in the health care and food industries. A growingconcern with preservatives has produced a need for new materials thatprevent microbiological contamination without including preservatives.The incidence of infection from food-borne pathogens is a continuingconcern and antimicrobial packaging material, utensils and surfaceswould be valuable. In the health care and medical device areas theutility of antimicrobial instruments, packaging and surfaces areobvious. Products used internally or externally in humans or animalhealth including, but not limited to, surgical gloves, implanteddevices, sutures, catheters, dialysis membranes, water filters andimplements, all can harbor and transmit pathogens. The polymers of thepresent invention can be incorporated into spinnable fibers for use inmaterials susceptible to bacterial contamination including fabrics,surgical gowns, and carpets. Ophthalmic solutions and contact lenseseasily become contaminated and cause ocular infections. Antimicrobialstorage containers for contact lens and cleaning solutions would be veryvaluable. Both pets and agronomic animals are exposed to and harbor avariety of infectious pathogenic organisms that can cause disease inanimals or humans.

[0278] An embodiment of the current invention is a antimicrobialcomposition comprising a facially amphiphilic polymer and a compositionselected form the group consisting of paint, coatings, lacquer, varnish,caulk, grout, adhesives, resins, films, cosmetic, soap and detergent.

[0279] Another embodiment of the present invention is an improvedcatheter, the improvement comprising incorporating or attaching afacially amphiphilic polymer therein or thereto.

[0280] Yet another embodiment of the present invention is an improvedcontact lens, the improvement comprising incorporating or attaching anamphiphilic polymer therein or thereto.

[0281] An embodiment of the present invention is improved plasticdevices for the hospital and laboratory the improvement comprisingincorporating or attaching a facially amphiphilic polymer therein orthereto.

[0282] A further embodiment of the present invention is an improvedwoven and nonwoven fabrics for hospital use the improvement comprisingthe incorporating or attaching a facially amphiphilic polymer therein orthereto.

[0283] The following examples will serve to further typify the nature ofthis invention but should not be construed as a limitation in the scopethereof, which scope is defined solely by the appended claims.

EXAMPLE 1 Polyamide FIG. 6 XIa

[0284] 2,6-Dinitro-4-t-butyl-phenyl (4-methyl)-benzenesulfonate (11)

[0285] 2, 6-dinitro-4-t-butyl-phenol (80 mmnol; 10) and tosyl chloride(80 mmol) were dissolved in 300 ml CH₂Cl₂. Diisopropylethylamine (DIEA,80 mmol) was added to the solution. The mixture was stirred at roomtemperature for 2 hours. The solution was washed with 10% citric acid,saturated aqueous NaCl (sat. NaCl), and dried with MgSO₄. The solventwas removed under reduced pressure, and the product was obtained as abright yellow solid in quantitative yield. ¹H NMR (500 MHz, CDCl₃):δ=8.12 (s, 2H), 7.80 (d, 2H), 7.40 (d, 2H), 2.51(s, 3H), 1.41 (s, 9H).ESI-MS: m/z: 417.2 (M+Na⁺)

[0286]2,6-Dinitro-4-t-butyl-1-(2-t-butoxycarbonylaminoethyl)-sulfanylbenzene(12).

[0287] Compound 11 (13 mmol), 2-Boc-aminoethanthiol (16 mmol) andDIEA(13 mmol) were dissolved in 50 ml chloroform. The solution wasstirred under nitrogen for 12 hours. The solution was washed with 0.5 MNaOH, 10% citric acid, sat. Na₂CO₃ and sat. NaCl, and dried with MgSO₄.The solution volume was reduced to 15 ml by rotary evaporation. Afteraddition of 80 ml hexane the product crystallized as a bright yellowsolid in. 94% yield. ¹H NMR (500 MHz, CDCl₃): δ 7.81(s, 2H), 4.87(s,1H), 3.31(t, 2H), 3.10(t, 2H), 1.44 (s, 9H), 1.39(s, 9H). ESI-MS: m/z:422.4(M+Na⁺).

[0288]2,6-Diamino-4-t-butyl-1-(2-t-butoxycarbonylaminoethyl)sulfanylbenzene(13)

[0289] Dinitro compound 12 (20 mmol) and sodium acetate (200 mmol) wereadded to 50 ml EtOH. The mixture was heated to 78° C., and the soliddissolved completely. Stannous chloride dihydrate (200 mmol) was addedto the solution, and the reaction mixture was stirred at 78° C. for 35minutes. After removal of solvent under reduced pressure, the residuewas dissolved in 800 ml EtOAc, and washed with 40% KCO₃. The organicphase was dried, evaporated and the residue column chromatographed(SiO₂) and eluted with a gradient of CH₂Cl₂/MeOH from 100:1 to 95:5 toproduce 13 in 93% yield. ¹H NMR (500 MHz, CDCl₃): δ 6.21(s, 2H), 5.41(s,1H), 4.35(br, 4H), 3.21(t, 2H), 2.75(t, 2H), 1.35 (s, 9H), 1.24(s, 9H).ESI-MS: m/z: 340.5(MH⁺).

[0290] General Method of Polymerization.

[0291] Diamine 13 (0.1 mmol) was dissolved in 3 ml DMF. Isophthaloyldichloride (0.1 mmol), triethylamine (0.2 mmol) ) andN,N-dimethylethylenediamine (0.2/n mmol)were added while stirring. Themixture was stirred under nitrogen for 18 hours. After the volume ofsolvent was reduced to 1 ml, water was added to precipitate the polymer.The polymer was collected and dried under vacuum. The Boc group wasremoved by treatment with trifluoroacetic acid (TFA, 3 ml) for 1 hour.The deprotected polymer was dried under vacuum overnight.

EXAMPLE 2 Solid Phase Synthesis of Oligomers XIb and XIc (FIG. 6)

[0292] Fmoc-PAL-PEG-resin (0.1 mmol) was swelled in DMF; then the Fmocwas removed with 20% piperidine in DMF for 20 min. The oligomer was thenbuilt up by alternately coupling 10 equivalents of isophthalic acid ordiamine 10. In each case the couplings were carried out in DMF using 10equivalents each of2-(1H-benzotriazole-1-yl)-1,1,3,3,-tetramethyluroniumhexafluorophosphate (HBTU) and N-hydroxybenzotriazole hydrate (HOBt),and 20 equivalents of DIEA for 24 hours at room temperature. Theoligomers were cleaved from the resin by treatment with TFA/anisole(95:5) for 1 hour. Pure oligomers were obtained by HPLC on a reversephase C4 column, with a linear gradient from 30% to 80% solvent B in 50minutes (solvent A, 0.1% TFA in water; solvent B, acetonitrile/water/TFA900:99:1). MALDI-TOF MS: XIb: 756.5 (M+H⁺), XIc: 1125.6.(M+H⁺).

EXAMPLE 3 General Method for Amide Polymerization

[0293] An oven-dried flask is charged with diamine dissolved indimethylsulfoxide (DMSO). To this solution is added an equimolarquantity of the diacid chloride which is freshly prepared by stirringthe dicarboxylic acid with excess thionyl chloride for 2 hr prior toaddition to the diamine solution. A catalytic amount of4-dimethylaminopyridine and four-fold molar excess of triethylamine areadded to the stirring mixture. The reaction is stirred at roomtemperature overnight under positive N₂ pressure. The DMSO solution ispoured into water and the solid polymer is recovered by filtration. Thedegree of polymerization is controlled by the addition of various molaramounts of a monofunctional amine. The molar amount of themonofunctional amine is determined by the Flory equation (G. Odian,Principles of Polymerization, John Wiley & Sons, Third Edition (1991)p.78-82).

EXAMPLE 4 General Method for Urea Polymerization

[0294] A dried flask is charged with equal molar ratios of the diamineand the diisocyanate in DMSO. The reaction is stirred at roomtemperature overnight under positive N₂ pressure. The reaction is pouredinto water or ether and the solid polymer is recovered by filtration.The degree of polymerization is controlled by the addition of variousmolar amounts of a monofunctional amine. The molar amount of themonofunctional amine is determined by the Flory equation.

EXAMPLE 5 Antimicrobial Assays

[0295] The inhibition studies will be carried out in suspension usingBHI medium inoculated with bacteria (10⁶ CFU/ml) in a 96-well format. Astock solution of the polymers was prepared DMSO/water and used toprepare a ten fold dilution series. Minimal inhibitory concentrations(MIC) were obtained by incubating the compounds with the bacteria for 18hours at 37° C., and measuring cell growth by monitoring at 590 nm.Antibacterial data is described in FIGS. 10 and 11.

EXAMPLE 6 Hemolytic Activity

[0296] The toxicity of the polymers to mammalian cells was evaluatedwith human blood, anticoagulated with 0.1 volume of sodium citrate,obtained from healthy volunteers. Washed erythrocytes are suspended ineither HEPES buffer, pH 7.4, containing 1 mM Mg²⁺ and 1 mM Ca²⁺ or inheated and unheated autologous serum obtained from clotted blood. Redcell agglutination will be evaluated microscopically and red cell lysiswill be evaluated by measuring the amount of released hemoglobinspectroscopically. The effect of polymers on platelet function will bestudied by adding increasing concentrations of polymer tocitrate-anticoagulated platelet-rich plasma. Platelet aggregation andsecretion will then be studied in a lumi-aggregometer (Chrono-Log).

[0297] All references cited in the application are hereby incorporatedin their entirety into this specification. Numerous modifications andalternative embodiments of the invention will be apparent to thoseskilled in the art in view of the foregoing description. Accordingly,this description is to be construed as illustrative only and is for thepurpose of teaching those skilled in the art the best mode of carryingout the invention. Details of the structure may be varied substantiallywithout departing from the spirit of the invention and the exclusive useof all modifications which come within the scope of the appended claimis reserved.

We claim:
 1. A polymer comprising a compound of formula I

wherein x is NR³, O, or S, y is C═O, C═S, O═S═O, or —C(═O)C(═O)— and R³is hydrogen, methyl or ethyl; either both A and B are independentlyoptionally substituted o-, m-, p-phenylene, or optionally substitutedheteroarylene wherein (i) A and B are both substituted with a polar (P)group and a nonpolar (NP) group, (ii) one of A and B is substituted witha polar (P) group and a nonpolar (NP) grand the other of A and B issubstituted with neither a polar nor a nonpolar group, or (iii) one of Aor B is substituted with a polar (P) group and the other of A or B issubstituted with a nonpolar (NP) group; or, one of A and B is o-, m-,p-phenylene or heteroarylene-the other of A and B is a C₃ to C₈cycloalkyl or (CH₂)_(q) where q is 1 to 7 wherein (i) one of A or B isoptionally substituted by one or more polar (P) group(s) and the otherof A or B is optionally substituted with one or more nonpolar (NP)group(s), or (ii) A is substituted with a polar (P) group and a nonpolar(NP) group and B is a C₃ to C₈ cycloalkyl or (CH₂)_(q) where q is 1 to 7and B is optionally independently substituted with one or more polar (P)or nonpolar (NP) group; R¹ is (i) -y-C and R² is OH or NH₂ wherein C isselected from a group consisting of C₁-C₆ allcyl, C₁-C₆ haloalkyl,vinyl, 2-propenyl, H-x-(CH₂)_(p)—, (C₁-C₆-alkoxy)C(═O)(CH₂)_(p)—, C₁-C₆alkoxy, benzyloxy, t-butoxy, pyridine and phenyl said pyridine or phenyloptionally substituted with 1 or 2 substituents independently selectedfrom a group consisting of halo, nitro, cyano, C₁-C₆ alkoxy, C₁-C₆alkoxycarbonyl, and benzyloxycarbonyl; or, (ii) is H and R² is-x-(CH₂)_(p)—W wherein x is as defined above and p is as defined belowand W is N-maleimide or V as defined below, or (ii) -y-C and R is-x-(CH₂)_(p)—W; or (iv) R₁ and R₂ together are a single bond; NP is anonpolar group an independently selected from R⁴ or —U—(CH₂)_(p)—R⁴wherein R⁴ is selected from a group consisting of hydrogen, C₁-C₁₀alkyl, C₁-C₆ haloalkyl, C₃-C₁₈ branched alkyl, C₃-C₈ cycloalkyl,monocyclic or polycyclic phenyl optionally substituted with one or moreC₁-C₄ alkyl, C₁-C₄ alkoxy or halo groups and monocyclic or polycyclicheteroaryl optionally substituted with one or more C₁-C₄ alkyl, C₁-C₄alkoxy, or halo groups and U and p are as defined below; P is a polargroup selected from a group consisting of IIIa, hydroxyethoxymethyl,methoxyethoxymethyl and polyoxyethylene —U—(CH₂)_(p)—V  (IIIa) wherein,U is absent or selected from a group consisting of O, S, S(═O), S(═O)₂,NH, —C(═O)O—, —C(═O)NH—, —C(═O)S—, —C(┘S)NH—, —S(═O)₂NH—, and C(═NO—)wherein groups with two chemically nonequivalent termini can adopt bothpossible orientations; V is selected from a group consisting of amino,hydroxyl, thio, C₁-C₆ alkylamino, C₁-C₆ dialkylamino, NH(CH₂)_(p)NH₂,N(CH₂CH₂NH₂)₂, amidine, guanidine, semicarbazone, C₁-C₆ alkoxycarbonyl,basic heterocycle, and phenyl optionally substituted with an amino,C₁-C₆ alkylamino, C₁-C₆ dialkylamino and lower acylamino optionallysubstituted with one or more amino, lower alkylamino or lowerdialkylamino; and the alkylene chain is optionally substituted with anamino or hydroxyl group or unsaturated; p is independently 0 to 8; m is2 to at least about
 500. 2. A polymer according to claim 1 comprising acompound of formula VII

wherein one of R⁹ or R¹⁰ and R¹¹ is a polar (P) group and the other ofR⁹ or R¹⁰ and R¹¹ is a nonpolar (NP) group; P is a polar group selectedfrom a group consisting of IIIb, hydroxyethoxymethyl,methoxyethoxymethyl or polyoxyethylene —(CH₂)_(p)—V  (IIIb) wherein: Vis selected from a group consisting of amino, hydroxyl, C₁-C₆alkylamino, C₁-C₆ diallcylamino, NH(CH₂)_(p)NH₂, N(CH₂CH₂NH₂)₂, amidine,guanidine, semicarbazone, imidazole, piperidine, piperazine,4-alkylpiperazine and phenyl optionally substituted with an amino, C₁-C₆alkylamino, C₁-C₆ dialkylamino and lower acylamino optionallysubstituted with one or more amino, lower alkylamino or lowerdialkylamino; and, the alkylene chain is optionally substituted with anamino or hydroxyl group; p is independently 0 to 8; and, m is 2 to atleast about
 30. 3. A polymer according to claim 2 comprising a compoundof formula IX

wherein: one of R⁹ or R¹¹ is either a polar (P) group or a nonpolar (NP)group and the other of R⁹ or R¹¹ is the other of a polar (P) group or anonpolar (NP) group; NP is —(CH₂)_(p)—R⁴ wherein R⁴ is selected from agroup consisting of hydrogen, C₁-C₄ alkyl, C₃-C₁₂ branched alkyl, C₃-C₈cycloalkyl, phenyl optionally substituted with one or more C₁-C₄ alkylgroups C₁-C₄ alkoxy or halo groups and heteroaryl optionally substitutedwith one or more C₁-C₄ alkyl group, C₁-C₄ alkoxy or halo groups and p isas defined below; P is a polar group selected from a group consisting ofIIIb, hydroxyethoxymethyl, methoxyethoxymethyl or polyoxyethylene—(CH₂)_(p)—V  (IIIb) wherein: V is selected from a group consisting ofamino, hydroxyl, C₁-C₆ alkylamino, C₁-C₆ dialkylamino, NH(CH₂)_(p)NH₂,N(CH₂CH₂NH₂)₂, amidine, guanidine, semicarbazone, imidazole, piperidine,piperazine, 4-alkylpiperazine and phenyl optionally substituted with anamino, C₁-C₆ alkylamino, C₁-C₆ dialkylamino and lower acylaminooptionally substituted with one or more amino, lower alkylamino or lowerdialkylamino; and, the alkylene chain is optionally substituted with anamino or hydroxyl group. p is independently 0 to
 8. 4. A polymeraccording to claim 3 wherein R⁹ is a polar side chain of a natural aminoacids and R¹¹ is selected from a group consisting of methyl, ethyl,n-propyl, iso-propyl, n-butyl iso-butyl, sec-butyl, tert-butyl,n-pentyl, iso-pentyl, sec-pentyl, and benzyl.
 5. A polymer according toclaim 3 wherein R⁹ is a nonpolar side chain of a natural amino acids andR¹¹ is a polar group selected from a group consisting of IIIb,hydroxyethoxymethyl, methoxyethoxymethyl or polyoxyethylene—(CH₂)_(p)—V  (IIIb) wherein: V is selected from a group consisting ofamino, hydroxyl, C₁-C₆ alkylamino, C₁-C₆ dialkylanino, NH(CH₂)_(p)NH₂,N(CH₂CH₂NH₂)₂, amidine, guanidine, semicarbazone, imidazole, piperidine,piperazine, 4-alkylpiperazine and phenyl optionally substituted with anamino, C₁-C₆ alkylamino, C₁-C₆ dialkylamino and lower acylaminooptionally substituted with one or more amino, lower alkylamino or lowerdialkylamino; and, p is independently 0 to
 8. 6. A polymer according toclaim 1 comprising a compound of formula I wherein: x is NH and y is C═Oor C═S; A and B are independently optionally substituted o-, m-, orp-phenylene, 2,5-thiophenylene or 2,5-pyrrolene; NP is a nonpolar groupindependently selected from R⁴ or —U—(CH₂)_(p)—R⁴ wherein R⁴ is selectedfrom a group consisting of hydrogen, C₁-C₄ alkyl, C₃-C₁₂ branched alkyl,C₃-C₈ cycloalkyl, phenyl optionally substituted with one or more C₁-C₄alkyl groups C₁-C₄ alkoxy or halo groups and heteroaryl optionallysubstituted with one or more C₁-C₄ alkyl group, C₁-C₄ alkoxy or halogroups and U and p are as defined below; P is a polar group selectedfrom a group consisting of IIIa, hydroxyethoxymethyl,methoxyethoxymethyl or polyoxyethylene —U—(CH₂)_(p)—V  (IIIa) wherein: Uis absent, O, S, SO, SO₂, or NH; V is selected from a group consistingof amino, hydroxyl, C₁-C₆ alkylamino, C₁-C₆ dialkylamino,NH(CH₂)_(p)NH₂, N(CH₂CH₂NH₂)₂, amidine, guanidine, semicarbazone,imidazole, piperidine, piperazine, 4-alkylpiperazine and phenyloptionally substituted with an amino, C₁-C₆ alkylamino, C₁-C₆dialkylamino and lower acylamino optionally substituted with one or moreamino, lower alkylamino or lower dialkylamino; and, the alkylene chainis optionally substituted with an amino or hydroxyl group; p isindependently 0 to 8;and, m is 2 to at least about
 500. 7. A polymeraccording to claim 1 comprising a compound of formula I wherein: x isNR³, R³ is hydrogen, and y is C═O or C═S; A and B are independentlyoptionally substituted o-, m-, or p-phenylene; NP is a nonpolar groupindependently selected from R⁴ or —U—(CH₂)_(p)—R⁴ wherein R⁴ is selectedfrom a group consisting of hydrogen, methyl, ethyl, n-propyl,iso-propyl, n-butyl, iso-butyl, sec-butyl, tert-butyl, n-pentyl,iso-pentyl, and sec-pentyl and U and p are as defined below; P is apolar group U—(CH₂)_(p)—V wherein U is absent or selected from a groupconsisting of O and S, and V is selected from a group consisting ofamino, lower alkyl amino, lower dialkylamino, imidazole, guanidine,NH(CH₂)_(p)NH₂, N(CH₂CH₂NH₂)₂, pyridine, piperidine, piperazine,4-alkylpiperazine; and p is independently 0 to 8; m is 2 to at leastabout
 500. 8. A polymer according to claim 7 comprising a compound offormula I wherein: x is NR³, y is CO, and R³ is hydrogen; A and B are m-or p-phenylene wherein (i) A is substituted at the 2-position with apolar (P) group and B is substituted at the 5-position with a nonpolar(NP) group, (ii) A is substituted at the 2-position with a polar (P)group and at the 5-position with a nonpolar (NP) group and B issubstituted at the 2-position with a nonpolar (NP) group and at the5-position with a polar (P) group or, (iii) A is substituted at the2-position with one of a polar (P) or nonpolar (NP) group and B issubstituted at the 2-position with the other of a nonpolar (NP) or apolar (P) group; NP is a nonpolar group independently selected from R⁴or —U—R⁴ wherein R⁴ is selected from a group consisting of methyl,ethyl, n-propyl, iso-propyl, n-butyl, iso-butyl, sec-butyl, tert-butyl,n-pentyl, iso-pentyl, and sec-pentyl and U and p are as defined below; pis independently 0 to 8; and, m is 2 to at least about
 500. 9. A polymeraccording to claim 8 comprising a compound of formula XII

wherein: NP is a nonpolar group independently selected from a groupconsisting of methyl, ethyl, n-propyl, iso-propyl, n-butyl, iso-butyl,sec-butyl, tert-butyl, n-pentyl, iso-pentyl, and sec-pentyl and U and pare as defined below; P is a polar group U—(CH₂)_(p)—V wherein U isselected from a group consisting of O, S, or no atom and V is selectedfrom a group consisting of amino, lower alkyl amino, lower dialkylamino,imidazole, guanidine, NH(CH₂)_(p)NH₂, and N(CH₂CH₂NH₂)₂, piperidine,piperazine, 4-alkylpiperazine; and, p is independently 0 to 8; m is 2 toat least about
 30. 10. A polymer according to claim 8 comprising acompound of formula XIV,

wherein: NP is a nonpolar group independently selected from R⁴ or —U—R⁴wherein R⁴ is selected from a group consisting of methyl, ethyl,n-propyl, iso-propyl, n-butyl, iso-butyl, sec-butyl, tert-butyl,n-pentyl, iso-pentyl, and sec-pentyl and U and p are as defined below; Pis a polar group U—(CH₂)_(p)—V wherein U is selected from a groupconsisting of O, S, or no atom and V is selected from a group consistingof amino, lower alkyl amino, lower dialkylamino, imidazole, guanidine,NH(CH₂)_(p)NH₂, and N(CH₂CH₂NH₂)₂, piperidine, piperazine,4-alkylpiperazine; and, p is independently 0 to 8; m is 2 to at leastabout
 30. 11. A polymer according to claim 1 comprising a compound offormula I wherein: x is NR³, y is CO, and R³ is hydrogen; A and B areo-phenylene wherein A is substituted at the 5-position with a polar (P)group and B is substituted at the 5-position with a nonpolar (NP) group;NP is a nonpolar group independently selected from R⁴ or —U—R⁴ whereinR⁴ is selected from a group consisting of methyl, ethyl, n-propyl,iso-propyl, iso-butyl, n-butyl, sec-butyl, tert-butyl, n-pentyl,iso-pentyl, and sec-pentyl and U and p are as defined below; P is apolar group U—(CH₂)_(p)—V wherein U is selected from a group consistingof O, S, or no atom and V is selected from a group consisting of amino,lower alkyl amino, lower dialkylamino, imidazole, guanidine,NH(CH₂)_(p)NH₂, and N(CH₂CH₂NH₂)₂, pyridine, piperidine, piperazine,4-alkylpiperazine; p is independently 0 to 8; and, m is 2 to at leastabout
 500. 12. A polymer according to claim 11 comprising a compound offormula XIII:

wherein: NP is a nonpolar group independently selected from a the groupconsisting of methyl, ethyl, n-propyl, iso-propyl, n-butyl, iso-butyl,sec-butyl, tert-butyl, n-pentyl, iso-pentyl, and sec-pentyl and U and pare as defined below; P is a polar group (CH₂)_(p)—V wherein V isselected from a group consisting of amino, lower alkyl amino, lowerdialkylamino, guanidine, piperazine, 4-alkylpiperazine; p isindependently 0 to 8; m is 2 to at least about
 30. 13. A polymeraccording to claim 11 comprising a compound of formula XV:

wherein either R¹² and R¹⁴ are independently polar (P) groups and R¹³and R¹⁵ are independently nonpolar (NP) groups substituted at one of theremaining unsubstituted carbon atoms, or R¹² and R¹⁴ are independentlynonpolar (NP) groups and R¹³ and R¹⁵ are independently polar (P) groupsNP is a nonpolar group independently selected from R⁴ or —U—R⁴ whereinR⁴ is selected from a the group consisting of methyl, ethyl, n-propyl,iso-propyl, n-butyl, iso-butyl, sec-butyl, tert-butyl, n-pentyl,iso-pentyl, and sec-pentyl and U is defined below; P is a polar groupU—(CH₂)_(p)—V wherein U is selected from a group consisting of O or Sand V is selected from a group consisting of amino, lower alkyl amino,lower dialkylamino, guanidine, pyridine, piperazine, 4-alkylpiperazine;p is independently 0 to 8; m is 2 to at least about
 30. 14. A polymercomprising a compound of formula II wherein

x and y can be (i) taken independently wherein x is NR³, O, S,(CR⁷R⁸)NR³, (CR⁷R⁸)O, or (CR⁷R⁸)S, y is C═O, C═S, O═S═O, —C(═O)C(═O)—,(CR⁵R⁶)C═O or (CR⁵R⁶)C═S, and R³ is hydrogen, methyl or ethyl; or, (ii)taken together to be pyromellitic diimide; and R⁵ and R⁶ together are(CH₂)₂NR¹²(CH₂)₂ and R¹² is selected from a group consisting of hydrogen—C(═N)CH₃ or C(═NH)—NH₂; and R⁷ and R⁸ together are (CH₂)_(p) wherein pis as defined below; both A and B are independently optionallysubstituted o-, m-, p-phenylene, or optionally substituted heteroarylenewherein (i) A and B are both substituted with a polar (P) group and anonpolar (NP) group, (ii) one of A and B is substituted with a polar (P)group and a nonpolar (NP) group and the other of A and B is substitutedwith neither a polar nor a nonpolar group, or (iii) one of A or B issubstituted with a polar (P) group and the other of A or B issubstituted with a nonpolar (NP) group; R¹ is (i) -B-y-R² and R² is-x-(CH₂)_(p)—W wherein x is as defined above and W is hydrogen, phenyloptionally substituted with up to three substituents selected from agroup consisting of halogen, C₁-C₄ alkyl, C₁-C₄ alkoxy, and carboxyl,N-maleimide, or V as defined below, and p is an defined below; or, (ii)R¹ and R² together are a single bond NP is a nonpolar group anindependently selected from R⁴ or —U—(CH₂)_(p)—R⁴ wherein R⁴ is selectedfrom a group consisting of hydrogen, C₁-C₂ alkyl, C₁-C₆ haloalkyl,C₃-C₁₈ branched alkyl, C₃-C₈ cycloalkyl, monocyclic or polycyclic phenyloptionally substituted with one or more C₁-C₄ alkyl, C₁-C₄ alkoxy orhalo groups and monocyclic or polycyclic heteroaryl optionallysubstituted with one or more C₁-C₄ alkyl, C₁-C₄ alkoxy, or halo groupsand U and p are as defined below; P is a polar group selected from agroup consisting of IIIa, hydroxyethoxymethyl, methoxyethoxymethyl andpolyoxyethylene —U—(CH₂)_(p)—V  (IIIa) wherein, U is absent or selectedfrom a group consisting of O, S, S(═O), S(═O)₂, NH, —C(═O)O—, —C(═O)NH—,—C(═O)S—, —C(═S)NH—, —S(═O)₂NH—, and C(═NO—) wherein groups with twochemically nonequivalent termini can adopt both possible orientations; Vis selected from a group consisting of amino, hydroxyl, thio, C₁-C₆alkylamino, C₁-C₆ dialkylamino, NH(CH₂)_(p)NH₂, N(CH₂CH₂NH₂)₂, amidine,guanidine, semicarbazone, C₁-C₆ alkoxycarbonyl, basic heterocycle, andphenyl optionally substituted with an amino, C₁-C₆ alkylamino, C₁-C₆dialkylamino and lower acylamino optionally substituted with one or moreamino, lower alkylamino or lower dialkylamino; and the alkylene chain isoptionally substituted with an amino or bydroxyl group or unsaturated; pis independently 0 to 8; m is 2 to at least about
 500. 15. A polymeraccording to claim 14 comprising a compound of formula II according towherein x=NH and y=CO; A and B are m- or p-phenylene wherein (i) A issubstituted at the 2-position with a polar (P) group and B issubstituted at the 5-position with a nonpolar (NP) group, or (ii) A issubstituted at the 2-position with a polar (P) group and at the5-position with a nonpolar (NP) group and B is either substituted at the2-position with a nonpolar (NP) group and at the 5-position with a polar(P) group or B is unsubstituted; NP is a nonpolar group independentlyselected from R⁴ or —U—(CH₂)_(p)—R⁴ wherein R⁴ is selected from a groupconsisting of methyl, ethyl, n-propyl, iso-propyl, iso-butyl, sec-butyl,tert-butyl, iso-pentyl, and sec-pentyl and U and p are as defined below;P is a polar group U—(CH₂)_(p)—V wherein U is absent or selected from agroup consisting of O and S, and V is selected from a group consistingof amino, lower alkyl amino, lower dialkylamino, imidazole, guanidine,NH(CH₂)_(p)NH₂, N(CH₂CH₂NH₂)₂, piperidine, 4-alkylpiperazine and; p isindependently 0 to 8; m is 2 to at least about
 500. 16. A compoundaccording to claim 15 where A is an optionally substituted1,3-diaminobenzene and B is an optionally substituted iso-phthalic acid.17. A polymer according to claim 15 comprising a compound of formula XI

wherein R⁴ is selected from a group consisting of methyl, ethyl,n-propyl, iso-propyl, n-butyl, iso-butyl, sec-butyl, tert-butyl,n-pentyl, iso-pentyl, and sec-pentyl; U is O or S; V is amino, loweralkyl amino, lower dialkylamino, guanidine; p is independently 0-8; m is2 to at least about
 30. 18. A polymer according to claim 15 comprising acompound of formula XVI

wherein: either R¹² and R¹⁴ are independently polar (P) groups and R¹³and R¹⁵ are independently nonpolar (NP) groups substituted at one of theremaining unsubstituted carbon atoms, or R¹² and R¹⁴ are independentlynonpolar (NP) groups and R¹³ and R¹⁵ are independently polar (P) groupsNP is a nonpolar group independently selected from R⁴ or —U—R⁴ where R⁴is selected from a group consisting of methyl, ethyl, n-propyl,iso-propyl, n-butyl, iso-butyl, sec-butyl, tert-butyl, n-pentyl,iso-pentyl, and sec-pentyl, and U is as defined below; P is a polargroup U—(CH₂)_(p)—V wherein U is absent or selected from a groupconsisting of O and S, and V is selected from a group consisting ofamino, lower alkyl amino, lower dialkylamino, imidazole, guanidine,NH(CH₂)_(p)NH₂, N(CH₂CH₂NH₂)₂, piperidine, and 4-alkylpiperazine; U is Oor S; V is amino, lower alkyl amino, lower dialkylamino, guanidine; p isindependently 0 to 8; and m is 2 to at least about
 30. 19. A polymeraccording to claim 15 comprising a compound of formula XX

wherein j is independently 0 or 1, R⁵ and R⁶ together are (CH₂)₂NH(CH₂)₂and R⁷ and R⁸ together are (CH₂)_(p) wherein p is 4 to
 6. 20. A polymercomprising a compound of formula IV

wherein: x is NR³ or NHNH and y is NR³, NHNH, S or O, and R³ ishydrogen, methyl or ethyl; z is C═O, —(C═O)C(═O)—, C═S or O═S═O; A and Bare independently optionally substituted o-, m-, p-phenylene oroptionally substituted heteroarylene wherein (i) A and B are bothsubstituted with a polar (P) group and a nonpolar (NP) group (NP), (ii)one of A and B is substituted with a polar (P) group and a nonpolar (NP)group and the other of A and B is substituted with neither a polar nor anonpolar group, (iii) one of A or B is substituted with one or two polar(P) group(s) and the other of A or B is substituted with one or twononpolar (NP) group(s), or, or (iv) A is substituted at the 2-positionwith a polar (P) group and at the 5-position with a nonpolar (NP) groupand B is unsubstituted; R¹ is (i) -B-y-R² and R² is -x-(CH₂)_(p)—Wwherein x is as defined above and W is hydrogen, pyridine and phenylsaid pyridine or phenyl optionally substituted with 1 or 2 substituentsindependently selected from a group consisting of halo, nitro, cyano,C₁-C₆ alkoxy, C₁-C₆ alkoxycarbonyl, and benzyloxycarbonyl; R¹ is H andR² is -x-(CH₂)_(p)—V or (ii) R₁ and R₂ together are a single bond; NP isa nonpolar group independently selected from R⁴ or —U—(CH₂)_(p)—R⁴wherein R⁴ is selected from a group consisting of C₁-C₈ alkyl, C₁-C₆haloalkyl, C₃-C₁₈ branched alkyl, C₃-C₈ cycloalkyl, monocyclic orpolycyclic phenyl optionally substituted with one or more C₁-C₄ alkyl orhalo groups, and monocyclic or polycyclic heteroaryl optionallysubstituted with one or more C₁-C₄ alkyl or halo groups and U and p areas defined below; P is a polar group selected from a group consisting ofIIIa, hydroxyethoxymethyl, methoxyethoxymethyl and polyoxyethylene—U—(CH₂)_(p)—V  (IIIa) wherein; U is absent or selected from a groupconsisting of O, S, S(═O), S(═O)₂, NH, —C(═O)O—, —C(═O)NH—, —C(═O)S—,—C(═S)NH—, —S(═O)₂NH—, and C(═NO—) wherein groups with two chemicallynonequivalent termini can adopt both possible orientations; V isselected from a group consisting of amino, hydroxyl, C₁-C₆ alkylamino,C₁-C₆ dialkylamino, NH(CH₂)_(p)NH₂, N(CH₂CH₂NH₂)₂, amidine, guanidine,semicarbazone, basic heterocycle, and phenyl optionally substituted withan amino, C₁-C₆ alkylamino, C₁-C₆ dialkylamino and lower acylaminooptionally substituted with one or more amino, lower alkylamino or lowerdialkylamino; and the alkylene chain is optionally substituted with anamino or hydroxyl group or optionally unsaturated; p is independently 0to 8; m is 2 to at least about
 500. 21. A polymer according to claim 20comprising a compound of formula IV wherein: x and y are NR³, z is C═Oor C═S, and R³ is hydrogen; A and B are independently optionallysubstituted o-, m-, or p-phenylene; NP is a nonpolar group independentlyselected from R⁴ or —U—(CH₂)_(p)—R⁴ wherein R⁴ is selected from a groupconsisting of hydrogen, C₁-C₄ alkyl, C₃-C₁₂ branched alkyl, C₃-C₈cycloalkyl, phenyl optionally substituted with one or more C₁-C₄ alkylgroups and heteroaryl optionally substituted with one or more C₁-C₄alkyl groups and U and p are as defined below; P is a polar groupselected from consisting of IIIa, hydroxyethoxymethyl,methoxyethoxymetbyl or polyoxyethylene —U—(CH₂)_(p)—V  (IIIa) wherein Uis O, S, S(═O), S(═O)₂, NH, or absent; V is selected from a groupconsisting of amino, hydroxyl, C₁-C₆ alkylamino, C₁-C₆ dialkylamino,NH(CH₂)_(p)NH₂, N(CH₂CH₂NH₂)₂, amidine, guanidine, semicarbazone, andimidazole, piperidine, piperazine, 4-alkylpiperazine and phenyloptionally substituted with an amino, C₁-C₆ alkylarnino, C₁-C₆dialkylamino and lower acylamino optionally substituted with one or moreamino, lower alkylamino or lower dialkylamino; and the alkylene chain isoptionally substituted with an amino or hydroxyl group; p isindependently 0 to 8; and, m is 2 to at least about
 500. 22. A polymeraccording to claim 20 comprising a compound of formula IV wherein x andy are NH, z is C═O; A and B are m- or p-phenylene and either (i) A issubstituted at the 2-position with a polar (P) group and B issubstituted at the 5-position with a nonpolar (NP) group, or (ii) A issubstituted at the 5-position with a polar (P) group and B issubstituted at the 2-position with a nonpolar (NP) group, or (iii) A andB are both substituted at the 2-position with a polar (P) group and atthe 5-position with a nonpolar (NP) group, or (iv) A is substituted atthe 2-position with a polar (P) group and at the 5-position with anonpolar (NP) group and B is unsubstituted; NP is a nonpolar groupindependently selected from R⁴ or —U—(CH₂)_(p)—R⁴ wherein R⁴ is selectedfrom a group consisting of hydrogen, methyl, ethyl, n-propyl,iso-propyl, iso-butyl, sec-butyl, tert-butyl, iso-pentyl, and sec-pentyland U and p are as defined below; P is a polar group U—(CH₂)_(p)—Vwherein U is absent or selected from a group consisting of O, S and V isselected from a group consisting of amino, lower alkyl amino, lowerdialkylamino, imidazole, guanidine, NH(CH₂)_(p)NH₂, and N(CH₂ CH₂NH₂)₂,piperidine, piperazine, 4-alkylpiperazine; p is independently 0 to 8;and, m is 2 to at least about
 500. 23. A polymer according to claim 20comprising a compound of formula XIV

R⁴ is selected from a group consisting of methyl, ethyl, n-propyl,iso-propyl, n-butyl, iso-butyl, sec-butyl, tert-butyl, n-pentyl,iso-pentyl, and sec-pentyl and U and p are as defined below; U isabsent, O or S and V is selected from a group consisting of amino, loweralkyl amino, lower dialkylamino, imidazole, guanidine, NH(CH₂)_(p)NH₂,and N(CH₂CH₂NH₂)₂, piperidine, piperazine, 4-alkylpiperazine; and, p is0 to 8; m is 2 to at least about
 30. 24. A polymer according to claim 20comprising a compound of formula XVII

wherein: either R¹² and R¹⁴ are independently polar (P) groups and R¹³and R¹⁵ are independently nonpolar (NP) groups substituted at one of theremaining unsubstituted carbon atoms, or R¹² and R¹⁴ are independentlynonpolar (NP) groups and R¹³ and R¹⁵ are independently polar (P) groupsNP is a nonpolar group independently selected from R⁴ or —U—R⁴ whereinR⁴ is selected from a the group consisting of methyl, ethyl, n-propyl,iso-propyl, n-butyl, iso-butyl, sec-butyl, tert-butyl, n-pentyl,iso-pentyl, and sec-pentyl and U and p are as defined below; P is apolar group U—(CH₂)_(p)—V wherein U is selected from a group consistingof O or S and V is selected from a group consisting of amino, loweralkyl amino, lower dialkylamino, guanidine, pyridine, piperazine,4-alkylpiperazine; p is independently 0 to 8; and, m is 2 to at leastabout
 30. 25. A polymer comprising a compound of formula XVIII

wherein: x=NH and y=CO; R¹ is (i) -y-C and R² is OH or NH₂ wherein C isselected from a group consisting of C₁-C₆ alkyl, C₁-C₆ haloalkyl, vinyl,2-propenyl, H-x-(CH₂)_(p)—, (C₁-C₆-alkoxy)C(═O)(CH₂)_(p)—, C₁-C₆ alkoxy,benzyloxy, t-butoxy, pyridine and phenyl said pyridine or phenyloptionally substituted with 1 or 2 substituents independently selectedfrom a group consisting of halo, nitro, cyano, C₁-C₆ alkoxy, C₁-C₆alkoxycarbonyl, and benzyloxycarbonyl; or, (ii) is H and R² is-x-(CH₂)_(p)—W wherein x is as defined above and p is as defined belowand W is N-maleimide or V as defined below, or (ii) -y-C and R² is-x-(CH₂)_(p)—W; or (iv) R₁ and R₂ together are a single bond; NP is anonpolar group independently selected from R⁴ or —(CH₂)_(p)—R⁴ whereinR⁴ is selected from a group consisting of hydrogen methyl, ethyl,n-propyl, iso-propyl, n-butyl, iso-butyl, sec-butyl, tert-butyl,n-pentyl, iso-pentyl, and sec-pentyl, C₁-C₅-haloallcyl and p is asdefined below; P is a polar group (CH₂)_(p)—V wherein V is selected froma group consisting of amino, lower alkyl amino, lower dialkylamino,imidazole, guanidine, NH(CH₂)_(p)NH₂, and N(CH₂CH₂NH₂)₂, piperidine,piperazine, 4-alkylpiperazine; p is independently 0 to 8; and, m is 2 toat least about
 30. 26. A method of killing microorganisms comprising thesteps of: Providing a substrate having disposed thereon a contactkilling, non-leaching facially amphiphilic polymer such that saidpolymer is not eluted from said surface; Facilitating contact betweensaid facially amphiphilic polymer on said substrate to allow formationof pores in the cell wall of said microorganism.
 27. A method accordingto claim 26 wherein said substrate is selected from a group consistingof wood, synthetic polymers, plastics, natural and synthetic fibers,cloth, paper, rubber and glass.
 28. A method according to claim 27wherein said substrate is from a plastic selected from the groupconsisting of polysulfone, polyacrylate, polyurea, polyethersulfone,polyamide, polycarbonate, polyvinylidenefluoride, polyethylene,polypropylene and cellulosics.
 29. A microbiocidal compositioncomprising facially amphiphilic polymer and a solid support selectedfrom a group consisting of wood, synthetic polymers, natural andsynthetic fibers, cloth, paper, rubber and glass.
 30. A method accordingto claim 29 wherein said solid support is a plastic selected from thegroup consisting of polysulfone, polyacrylate, polyethersulfone,polyamide, polycarbonate, polyvinylidenefluoride, polyethylene,polypropylene and cellulosics.
 31. A method for identifying faciallyamphiphilic polymers comprising: (1) selecting a polymer backbones orscaffolds suitable for regiospecific introduction of polar (P) andnonpolar (NP) groups; (2) determining parameters for a molecularmechanics force field utilizing ab iizitio quantum mechanicalcalculations; (3) calculating energetically accessible conformations ofsaid backbone using molecular dynamics or molecular mechanicscalculations; (4) identifying energetically accessible conformations ofsaid backbone wherein the periodicity of a geometrical/conformationalrepeat matches a sequence repeat; (5) synthesizing monomers with polarand nonpolar substituents; (6) synthesizing an antimicrobial polymercontaining said monomers by solution or solid-phase synthesis.
 32. Aprocess for producing an antimicrobial surface by attaching aantimicrobial facially amphiphilic polymer to a surface comprisingtreating said surface with a first chemically reactive group andreacting a facially amphiphilic polymer linked to a second reactivegroup thereto.
 33. A process according to claim 32 where said firstreactive group is a 1-(trialkoxysilyl)propylamine and said secondreactive group is an activated carboxylic acid.
 34. A process accordingto claim 32 where said first reactive group is a ω-(trialkoxysilyl)alkylbromomethylacetamide and said second reactive group is a thiol.
 35. Aprocess according to claim 32 where said first reactive group is aN-[ω-(trialkoxysilyl)alkyl]maleimide and said second reactive group is athiol.
 36. A process according to claim 32 where the first reactivegroup is a gold surface and said second reactive group is a thiol. 37.An antimicrobial composition comprising a facially amphiphilic polymerand a composition selected form the group consisting of paint, coatings,lacquer, varnish, caulk, grout, adhesives, resins, films, cosmetic, soapand detergent.
 38. An improved catheter, the improvement comprisingincorporating or attaching an antimicrobial facially amphiphilic polymertherein or thereto.
 39. An improved contact lens, the improvementcomprising incorporating or attaching an antimicrobial faciallyamphiphilic polymer therein or thereto.
 40. Improved plastic devices forthe hospital and laboratory the improvement comprising incorporating orattaching an antimicrobial facially amphiphilic polymer therein orthereto.
 41. Improved woven and nonwoven fabrics for hospital use theimprovement comprising the incorporating or attaching an antimicrobialfacially amphiphilic polymer therein or thereto.